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You have difficulty sliders in the option menu if you want to do it while being mostly afk/not trying.
Hope that help.
unlock a couple of good items on D1 and then jump straight to D5
for example Golem is a nightmare if you first dont unlock Masochist weapon
Once you know your way low Danger levels become a chore
ive only completed wave 20 on 7 classes and 2 of them are D5, ive just moved one danger up for every run i completed but now that im trying a bunch of different classes im not getting anywhere on D5
Renegade item is extremely broken imo , and more those are better to just do in low Danger levels so then you can use them at Dange 5
but I have 70% all done in D5 and the rerst 20% on low danger and 10% not completed more or less
Synergies of unlocks with the classes they represent are mostly thematic and often don't help to win the run.
Find an item list somewhere and check whether you want certain unlocks or not.