This is something I thought about but the one that I think would destroy the Marvel Universe is Spider-Man.
While many of you would think "Hell No!" but here's how it would happened.
In old Spider-Man comics (don't know which one), Norman Osborn wanted Peter Parker to be his heir instead of Harry but failed. In this, What if Norman succeeded? What if Norman sucessfully broke Peter to the point that he did became his new heir, but something bad happened which led to Norman ultimately regretting his decision and Peter becomes something far worse that Peter would destroy the Universe as the Red Goblin, leaving Norman's decision to recruit both Heroes and Villains to stop him. This would be one man versus the entire universe, but ultimately the one who might be capable of stopping Peter is Harry as the New Spider-Man.