Immortal Redneck

This achievement may look pretty damn difficult at first, but don't worry, there is a way to make this WAY easier.

Plague Medallion makes every enemy die in one hit, but so will you, as you only have 1 point of health, requiring you to be extremely cautious when entering new rooms. So what's the solution?

First thing you want to do is run through the third pyramid normally like you would, with whatever character you want, preferably after you have maxed or at least nearly maxed your skill tree. Explore every room on every floor, collect as much gold as you can (you'll need it later) and make note of which chests contain useful scrolls and accurate, rapid-fire weapons such as the assault rifle.

After beating the pyramid, make sure you have unlocked and upgraded Seth, we're gonna be playing as him during the Plague run, so change into him and go to the merchant, buy Deja Vu and as much good scrolls as the money you racked up allows you to (I got 8 when I attempted this). Equip the Plague Medallion and enter the third pyramid again. The Deja Vu will make sure your map is uncovered and everything is just the same like during your last run and good scrolls will hopefully net you some neat bonuses (scroll reject bonus comes in handy in case you accidentally pick up something shitty).

You're playing as Seth, whose active skill makes this a breeze, because he sends out a pulse that damages every enemy in vicinity, and since they die in one hit, it clears majority of rooms in one blast. Always wait for it to recharge before entering a new room. Be cautious, don't charge, make sure no enemy sneaks up on you and rush for the stairs whenever you can, taking only short detours in case chest room is near and you're sure it contains something useful. Like I said, something like assault rifle will come in handy, because you can unleash a hail of bullets on whatever enemies weren't caught in your active skill pulse.

During the boss fight on third floor, quickly dispatch the generators with your weapon and immediately unleash your active skill pulse to get rid of the pesky enemies (watch out for disco ballers, you can get caught in their beams quite easily if you're not quick enough). Once the boss allows you to damage him, do so, and it's over for him. Final boss is laughably easy, as you only need to hit him with one bullet and he almost always starts out in the open and takes a bit of time before he starts attacking. Boom, achievement unlocked. Wasn't that hard, was it?