Neon Abyss

As the description says, you need to finish a run without taking a single hit of damage (whether it be to hearts or shields). This is one of the hardest achievements in the game, but there are actually some things you can do to make this far easier than it otherwise would be, making it pretty manageable for even average gamers.

First, do this on a new save file. From the main menu, choose Save Slot and pick an empty one. The reason for this is because you want your run to only consist of the first five floors. After you beat Argus, the run is six floors, and after Hal, seven floors. You want the run to be as short as possible.

Second, play through the tutorial (remap the controls if need be), obviously choose Easy difficulty, and after you beat the boss, quit back to the bar.

Third, and this is extremely IMPORTANT, go kill yourself in two runs on Easy. This will drop the difficulty from Easy with three dots to Easy with one dot, if you look at the difficulty poster in the bar. The more dots above the difficulty, the harder the game is. Dying takes dots away, so kill yourself twice to drop it from three dots to one dot. You can now play Easy one dot, which is the easiest difficulty in the game.

With the setup done, you now need to beat each floor without getting hurt. While this is no walk in the park, it's far, far easier on Easy one dot. Enemies barely pay you any attention, and bosses aren't very aggressive. Since you can't get hurt for this achievement, focus all of your items and boss drops on attack strength. Don't pick up heart containers, always go for gun and damage upgrades, and take any items that improve damage. You want to make boss fights as quick as possible to reduce the likelihood of getting hit.

It should go without saying, but if you do get hit at all, use the Save Reload Exploit to start the floor over again. Layout, enemies, boss, items, etc., don't change, allowing you to learn and improve each time you have to retry a floor. If you find a room or two to be an absolute pain to clear without getting hit, don't bother with that room (if you can avoid it and get to the boss a different route). Most bosses will be very quick and easy on this difficulty and with upgrades. George can be a pain in the beginning with the projectiles he shoots, and the Goddess of Makeup can be annoying if your range isn't enough to reach her while still safe across the room, but all other bosses are pretty simple to learn their attack patterns and avoid them. Boss fights shouldn't take more than a minute or so on this difficulty, so you don't have to dodge for long.

The fight against Argus will be the hardest part of this run. You definitely want to get as many upgrades as you're comfortable with along the way in previous floors, because that'll make this fight as short as possible. The first phase of this fight is pretty easy to do without getting hit, but those tentacle wire things in the second phase give you virtually no time to react and can ruin things. Hopefully, with enough upgrades through your run, you only need to dodge the wires for two or so cycles before you finish him off. Some luck is almost required here, hoping you get a good wire pattern that's easy to avoid in a split second. Expect to have to restart this floor a few times to nail it, but once you do, you'll unlock this achievement.