This guide's going to cover the route itself as well as strats for all three categories of the game (Easy/Normal/Very Hard). Different strategies for Normal and Very Hard will be written as deviations from the Easy strats, and all levels mentioned are for Easy. Expect the numbers to be higher on higher difficulties.

Factory 1

Spin slash the enemy here. Once you're outside, spin slash the two raptors. Slash the mummyheads three times, then spin slash, then stab. That combo will kill them on easy but on higher difficulties they'll take a bit more so do some more regular slashes before the spin. Viola 1 will show up now. Let her approach you, then grab her and throw her into the floor. Follow that up with a stab. If your angle is close enough to perpendicular with the floor, this is enough damage to kill her.

Grab the item in the center of the room. Turn around and fire a charge shot at the two Lv1 enemies that were behind you without locking on. Ideally you hit the raptor and that kills him, then fire a second one at the mummyhead (which you are locked onto now) and finish him off with homing lasers. Chances are this won't work and you'll have to fly up to the group and finish them off after this with whatever works. Head left and grab the item in the ditch below the group of enemies (you may have to go around a little bit on higher difficulties to avoid the encounter).

Town 1 (Tempest)

Get close to Tempest to bait out his close range fire attack, but stay far enough away that it doesn't hit you. Spam small shots for the first half of his HP bar. Hold up (Triangle/Y) so that you don't fall too low to hit him.

For his second half, get up right in front of his face as high as you can and hit him with charge shots. Three shots is enough to kill on easy, but on normal you'll need a fourth shot (he will fly up into the air then drop down) and on Very Hard it will take a third cycle.

Factory 1

Turn to the corner behind you and to the right. Fire a charge shot at the Lv2 group back there. You are aiming for the guy in front, who is the leader. Afterwards, use homing lasers and regular small shots to kill the rest of the group from a distance. The leader will need another hit from something to kill on higher difficulties. Go the corner opposite the one the enemies were in and grab the item in the ditch.

City 1 (Pillar)

Just come here and leave.

Town 2

Destroy the porters in the order shown in this screenshot You can fire homing lasers at them as you're approaching to try to get extra hits in and speed things up, or just fly to them and use small shots. Regardless, lock on doesn't work here so good luck. You'll get an encounter with Lv2 raptors at around the fourth pillar, just don't lock onto them and hope they go away. Once all the porters are gone, the sniper will appear in a box at the yellow circle on the image. On easy, if you move fast enough you can grab the sniper without starting an encounter with the Lv1 mummyheads. This is unavoidable on higher difficulties.

City 1

Shoot the targets on the pillar. On PS3/x360, you can shoot through the pillar to hit targets on the other side. On PS2, you have to wait for them to spin around to where you can see them. You should have 12 ammo left if you don't miss any shots.

EPS2

The entrance to the tunnel is in the back right corner of the room. Go in there, run up to the wall you can't get through, and then exit. Outside the tunnel, turn around and head for the Lv3s Passcode guys in the distance. Hit the guy in front with a charge shot from a distance, then finish them off with spin slashes. Try not to get ganged up on (this is a big problem on Very Hard). If you can kill the front guy (he's the highest level) with a second charge shot before the group reaches you, that's perfect.

Town 1

Grab the metatron in the blue box in front of you to the left if you got owned by the last group of enemies. Head for the back of this area, your target is the stationary group of three Lv3s passcode mummyheads. When you get close, try hitting the bottom one with an untargeted charge shot (do not bother on Normal/VH). These guys will kill you if you don't split them up, so force them apart by spamming homing lasers and stabs. Once a mummyhead is far enough away from the other two that they can't hit you, feel free to kill it however you want.

EPS1

The entrance to the tunnel is in the back right corner of the area. Go through the tunnel to the generator, spin slashing all the enemies. The second enemy (a mummyhead) can be grabbed, thrown, and stabbed for on Easy. Destroy the generator by hitting the glowing blue face of it (but not the center) with homing lasers, then leave. On your way out, go down the left path you ignored earlier to get the item. Grab+Stab the last enemy on the way out on Easy.

Town 2

Fly to the two broken robots on the ground, in the same place where you got the sniper earlier. On Easy, you can slip between two groups of enemies to get the raptor without starting an encounter (this pic shows about where you want to fly). On higher difficulties, don't bother trying this and just hope the enemies let you run away quickly.

EPS2

Head into the tunnel. The raptor's stationary charge slash is your most powerful attack, but a basic melee combo and stabs are also very effective. Instead of going straight towards the generator, go down the path you see to the right and grab the item down there first. You can destroy the generator with a single charge shot.

Leave Town 2 as Jehuty, go to EPS2, kill the raptor in the tunnel, and then leave the area. Fly towards Mountain 1 and leave the area you appear in when you get shot down.

Factory 2

Go inside the factory and kill the Lv1 however you want. Do not underestimate him on VH. Grab the item on the left.

City 2

Your target is the two Lv5s enemies to your right. You can try to fire a charge shot at them before locking on, but spin slashes will work fine.

Town 3

The enemies with the passcode you need will not spawn until you kill the invisible Lv4 group to your left (circled here, see from where you enter the area). You can try to kill the weak raptor in this group with a charge shot. Once they're dead, an invisible Lv2 Passcode group with appear right by where you probably started the Lv4 fight. If you know where they spawn, you can time a spin slash to hit them all right as they appear.

Factory 2

Grab the metatron right in front of you if you aren't at full health (ESPECIALLY on higher difficulties, you can ignore it on Easy). Snipe the four porters way off in the distance on your left (they are the green dots, get a little closer and let the auto-aim help you out). Then turn around, shoot the two in the corner, the four floating above the warehouses, and the two far ones on the right. Be careful where you're standing when shooting those last six porters on higher difficulties, or you'll get your target stolen by an encounter when you're trying to aim. You should have 1 sniper ammo left, if you haven't missed any shots so far this run. Go back into the warehouse, kill the guy, and get the item. Leave the warehouse, grab the decoy ammo from the box in the opposite corner to where you entered the area, and leave.

Park 1 (Tyrant)

Get closer to where you can actually hit him. Place a decoy as soon as he starts targeting you with the big laser, then move aside slightly and hit him in the face with charge shots. On all difficulties, you should have him at half health by the time he's done firing the required two giant laser shots.

As soon as the second half starts, dash into the center of him to cancel his flying around. Tyrant has three attacks, the first one is lasers that you can avoid by standing over his left arm. While you're there, you can hit him in the face with two charge shots and some small shots. This is enough to kill him on Easy. On Normal, let him smash into you again and then finish him off while he fires the missiles. On Very Hard, this fight will go on for a few more cycles, and I don't recommend letting him smash into you more than once. His third attack, which you should only ever see on Very Hard, is some homing stun balls that you can destroy between attacks by just shooting them. The easiest way to dodge his flying around is to change your height while doing it.

Mountain 1

The blue box right in front of you is metatron, grab it if you need it (you won't get more until the second group). This is a mostly linear area. I recommend looking at a video for the route but all you really need to know is that you turn right after destroying the first wall, and left after destroying the second. Use spin slashes to deal with all the enemies in this area, and on the second and final groups make sure you kill the leader (he has a *) first. The last two groups of enemies in this area are high enough level to use a powerful counter attack that deals a ton of damage, even on easy.

Nebula

As soon as the fight starts, go up and try to get as many small shots as you can. Once he's done flying around outside, hit him with a charge shot as he flies back into the arena. then get up close and spam small shots. Try to stay outside the rotating cone of lasers, and try to avoid the homing attacks if possible. On Easy and Normal, you can kill him during this cycle, but on Very Hard he will fly away. Hit him with 3-4 charge shots when he comes back (his second cycle is just standing still for some reason), then repeat the small shot strat on the third cycle to finish his first half.

From where you start the second half, move up as high as you can but don't go anywhere. When Nebula drops down in front of you, fire a charge shot at him as he's turning to face you. This should cancel his attack, and automatically change your target to the weak spot on his butt. Fly down there and hit him with 3-4 charge shots. Repeat this until he dies. You can tell you got the cancel because he will scream when you hit him in the head, although sometimes he will still attack after that. On Easy and Normal this takes two cycles if you get all four hits in, on Very Hard it will take four perfect cycles.

As a side note, this fight will lag like hell on PS3 but run fine on PS2 and x360. I estimate that it's about 20 seconds lost to slowdown/lag on easy and even more on Very Hard.

Viola 2

The best strat to use here is to grab her and throw her against the boxes or the wall. If you angle is close to perpendicular, she will get stunned for a moment and you can regrab her and repeat. This is very difficult, and what most of your practice with the game will go towards. It is important to know which of her attacks can be punished with a grab, and how to properly dodge each of them. I recommend watching this clip by DaisyFan for a good demonstration of how the fight should be done. Getting a Grab+Throw then stabbing her is a good way to get through the first part of her health fast.

Bomb Defusing

On Easy, you will be destroying the bombs instead of defusing them. This will drop your health to near-zero, so don't try it if you aren't at 80% health or better. The final enemy of each group (except for the third group with the two Lv5s cyclopses) will drop metatron, so what you should do is keep one enemy alive but weakened so that you can kill him as soon as you blow up a bomb for a full heal. Make sure you separate the mummyheads (2nd group) with stabs or they will deal too much damage to you, and you won't be able to blow up the bombs anymore. If you're particularly far from one of the bombs, you can use that last sniper ammo you've got to hit it from a distance, otherwise homing lasers are the projectile you should use.

On Normal and Very Hard, shooting a bomb will kill you instantly, so don't try it. Instead, defuse them like you're supposed to. On Very Hard, you should seriously consider using your three leftover decoys to distract the enemies while you defuse the first three bombs.

Zombie Neith

Dash up to her, and try to grab her and throw her into the wall behind where she first appears. Once you've got her against the wall, you can repeatedly grab and throw her into the wall for an "easy" kill. Make sure you are very close to her and that she is pressed up against the wall, so that you regrab her as she is trying to get out of the tight spot you've put her in. Otherwise, she can escape.

Anubis

Just wait a minute and the game ends. You can't die so just do whatever you want. Congrats! You've finished a speedrun of Zone of the Enders.