The MU have done elseworlds: Ruins, 1602, Noir, Marvel Fairy Tales (which is underrated especially Spider-Man Fairy Tales which actually uses fairy tales to make some interesting observations on the characters), and right now you have Chip Zdarsky's Spider-Man Life Story which could launch a series of elseworlds that look at the Marvel Universe if it remained in real-time from the '60s to the present day.
My takes.
I'd like to see how Spider-Man, Daredevil, and others will look if it was set in the Gangs of New York. You know iconic movie, great period setting, good historical background (the period leading to and following the Civil War). This would work best as a street story. I think. But think of do Matt Murdock as an actual Irish Catholic immigrant to New York in this horrible period where New York housed the worst slum in the world, and it was run by Boss Fisk, and you could bring in Captain America who supports the Union and has to put down the Draft Riots because of the race riots and the whole class issue of Unon enlistment of Irish immigrants and so on.
One Elseworld I am pitching...Doctor Doom versus Napoleon or Alexander. Basically have Doctor Doom in an Alternate Universe or whatever go up against a real-world historical conqueror. Level the field, like maybe Napoleon gets access to tech via Kang the Conqueror or whatever. But have them tussle and see how it turns out. Doom has fought King Arthur you know, so why not Caesar, why not Alexander and so on. I once did a presentation about Archimedes and Hannibal Barca in the second Carthaginian War (Archimedes was on Hannibal's side in real history). So you do have precedent of scientists and conquerors teaming up, so why not the scientist-conqueror. Doom's basically this great European Marvel character and tied to this rich side of European history from the medieval to the modern so you can work him with that.