Difficulty matters a lot.

The main differences have to do with enemy aggression and damage modifiers. On Hell, there's a 25% damage penalty to damage dealt by the player, and a 25% buff to damage dealt by enemies. On Easy, enemies have about a 40% damage penalty and their aggression is lowered sharply. There are also some mechanics changes on Hard/Hell, such as poison ticks being able to KO.

So no, the difficulties are actually a fair bit different and are not comparable. FWIW, the top runs are done on Hell currently. That's not because it's faster, but because that's the more interesting way to play the game IMO.

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