What villains do you think would win if it weren't for them having to lose due to being written to lose. I can think of 3 right off the bat though each would need The Prep which they almost always have in order to do it.
These are the 3 smartest minds and I think they would win if they were allowed.
Doctor Doom is the 2nd smartest man in the Marvel Universe(or tied for first if you ask certain people or base it on feats), has the most powerful tech on Earth, a country full of powerful warriors, and is Earth's most powerful sorcerer. With Prep he if allowed would murder stomp the Fantastic 4.
Loki is the most cunning being in the Marvel Universe and if given Prep would not just be able to conquer Asgard but also many other places.
Lex Luthor is the smartest man in the DC universe and with Prep he not just should be able to beat Superman, he should beat Batman(even if he had Prep as well), Wonder Woman, Green Lantern, Flash, and almost any other DC universe superhero.
Can you think of anyone you would add to this list?