reroll those weapon abilities (or find them) until you break the game. get that +80% damage to poisoned enemies on your sadist's stilleto and find a reliable way to poison enemies before you stab them. you should be one- or two-shotting mostly everything except bosses throughout the whole run if your build is good

it also helps to make several "unlock only" runs where all you do is get the hunters grenade and throw it at the first enemy that has the grenade icon over their head. you'll get a lot of outfits this way but you'll eventually run out of outfits to unlock and start getting strong weapons and mutations. i picked up the game again about a week ago and dedicated about 15 runs to unlocking and got a lot of weapons and mutations i didn't even know existed

leveling up the forge on BC1 is effective too. take your time and clear out every biome for max cells and don't spend any until you beat the first boss, then dump all your cells into the forge. strong weapon spawns with multiple effects are key to finding broken synergies that allow for deep runs

lastly — and this has been mentioned before in this thread — try to focus your build on one color so you can output max damage *and* get giant HP boosts in the last few levels. a good build looks something like

4 brutality
12 tactics
3 survival

with the 2 survivals being picked up on the last biome for a +110% HP boost and the 3 brutality being picked up here and there for HP boosts when you feel like you're too fragile. you can also reset mutations just before the final boss and select "dead inside" for another 50% HP boost