Notable tactics during runs: With your red suit, zip your way through with either a quick B+A web zip or a diagonal web zip. This is what you'll be using for the majority of the run for movement. Only save when you're running low on health. Throwing items at enemies can help, especially in Residential where they can one-shot most enemies. Utilize combat to the best of your abilities (especially for bosses, get them into a loop if possible via corner beatdowns or keeping them airborne as long as possible). And when doing boss battles, its preferred that you pick Goblin (if you've helped him at least once), as he's the fastest attacker. Try not to go for Black Cat (unless absolutely necessary), you want every bit of damage possible.

Residential: Go for the first Early Damage Upgrade. When the first boss is defeated, hope you get the shorter dialogue of "I feel stronger!", saving a couple of seconds. And when picking up the big object in the boss room, hope you get the slide movement to just fall through and not have to throw it.

Sewers Pt. 1: When in the power room and when the barrier opens, go for a quick B+A web zip across for faster movement. Repeat this for shutting off the water. Refer to Drain Fight Skip.

Pier: "Talk" with Black Cat and decide who you're going to help. For those who aren't confident to go without the EXP earned in this sidequest, I'd recommend helping Green Goblin but if you're quick with Roll Dodges, then try Nightskip 2. Otherwise, refer to Allies Skip. After defeating the blue symbiote boss, make your way to the room previously protected by the orange wall and beat enemies there. This makes things easier for when you later have to destroy the symbiote portals.

Downtown Pt. 1: Get rid of the dumpster for your exit to the Sewers later. Then its business as usual with enemies and bosses. Once done, make your way back down to Sewers.

Sewers Pt. 2: Your short trip here is basically going down from the station and defeating the boss. Then going back up to Residential for Downtown again.

Downtown Pt. 2: Business as usual. Although the boss here is quite a tricky one, being very quick. Once meeting with Black Cat again, it's highly recommended that you go and "help" Nightcrawler (read the Nightskip guide for more info). After helping either NC or Goblin, make your way to the hive.

Hive Pt. 1: Another short trip. Surprise Venom with a web attack as he would have done to you, and defeat him. Exit the Hive to dispose of the symbiote portals.

Symbiote Portals: The ideal route to take based on the TAS is this: Residential, Downtown, Pier, and Sewers. Then return to the hive for the last time.

Hive Pt. 2: Nothing new here up until the final boss, the Symbiote Leader (or Mega Venom, as known by his files apparently). This is where you'll want to be efficient with your combat. His first stage is pretty standard, indicated by his first bar. Second stage has him be very defensive, and afaik, there's no known way to manipulate his ai into rejecting those tactics. So you can only land hits when he attacks. Using Nightcrawler might help in order to land more hits in the air. Once he's down a certain amount where you can get him airborne, keep him there as much as possible. Once down, exit the hive and its game over.

Provided below is the TAS for reference and visuals of the description above, which will help those doing any% runs as to which upgrades and collectibles might be necessary. (of course, remember that TAS's are NOT allowed in this site):