This, or even a Path of Exile style, less-RNG dependent mode of run, maybe with core Nemesis enemies or whatnot who you’d variously need to survive attacks from, protect NPCs against, or force to flee (and, eventually, you’d of course kill).
Or, heck, a mode where multiple maps collide, with known bosses and powers drop sets therein, so you’d try to chart a best-guess optimal course between knowns and unknowns.
Those are both, obviously, far more time-intensive to design, though…