5. Lex Luthor
Pretty much the original uber-villain, Lex Luthor was the unlikely antagonist to Superman - and Lex was nothing more than a bald business guy who just really didn't like the Man of Steel (an earlier origin story for Luthor revealed that it was Superman's fault he went bald, and THAT was his motivation for hating Supes). Sure, he was a charismatic, ultra-wealthy genius (who briefly served as President of the United States), but fate certainly dealt him a much different hand than it dealt Kal-El. Luthor has tried a myriad of techniques to defeat his nemesis - kryptonite everything, creating Bizarro and Metallo, an Orange Lantern ring, etc. - but has never quite made it. The beauty is that Lex thinks he's the hero - Superman is an ultra-powerful alien that could rule the world if he decided he felt like it, whereas Lex uses his superior intellect to develop new technologies and is, ya know, a human being from Earth. So the next time one of your relatives starts complaining about immigrants, just remember they're basically channeling Lex Luthor.
4. Dr. Doom
Another supergenius on this list of villains, Dr. Victor von Doom, ruler of Latveria, has served as the chief antagonist to the Fantastic Four since almost their very beginning. His primary adversary, though, has always been Reed Richards (aka Stretch-Guy) - the only person in the Marvel universe Doom fears may be more intelligent than himself. His desperate pride has always been his greatest flaw - he needs to be worshipped, feared, and respected by all. Although one would imagine a man covered in metallic armor would inspire more fear and awe than a guy in metallic armor covered in a green slanket.
Venom is a nightmare version of Spider-Man - it looks very similar to Spidey, but with enormous muscles, a mouth filled with sharp fangs, and a huge slobbering tongue always being waved around. Born after Spider-Man rejected the alien symbiote and it attached itself to Eddie Brock, it fused two beings that already hated Spider-Man into a single entity that REALLY hated Spider-Man. What's great about Venom is it represents another of Peter's failings in regards to the ol "With great power comes great responsibility" maxim - Peter was exposed to even greater power with the symbiote, which he abused and allowed himself to lose control. As a result, he spurned the symbiote entirely, making himself responsible for the creation of his own villain - as well as its offspring, Carnage. With all of the destruction and death the symbiotes have caused, it all weighs on the conscience of poor Peter Parker, who just wanted to win some wrestling money.
There are probably the most obvious parallels between real world social issues and comic book stories in X-Men - where mutants are stand-ins for any oppressed group throughout time. All oppressed groups will stand up for themselves after years of discrimination, and usually they will rally around a strong leader who wants to institute some lasting change - in the case of the mutants in X-Men, that person is Magneto, and the lasting change is "murder all non-mutants." Magneto suffered oppression even before his mutanthood, as a Jewish survivor of the Holocaust, so he knew the depths of humanity's potential for outright hatred to anyone viewed as 'different.' And, in practice, his philosophy seems a lot more likely than Xavier's belief that humans and mutants can just get along - humans are probably never going to warm to a species that so wildly outpowers them in every regard, where individual mutants could singlehandedly destroy the entire planet. Over the years, he crossed over into outright villainy in trying to achieve his goals - notably, he's torn out Wolverine's adamantium from his skeleton - but he's always been understandable in a way few villains are. Humans have committed some horrible acts against mutants in the X-Men universe - it's hard not to root for Magneto sometimes. You gotta feel at least a little bit of sympathy for him for having to wear that stupid bucket on his head.
The Joker doesn't have any interest in money, power, fame, respect, or even life. The Clown Prince of Crime has one interest: Batman. The two are distorted reflections of one another, which the Joker sees a lot more clearly than Batman. But whereas the Joker has accepted and reveled in madness, Batman refuses, despite the ample evidence - he's a billionaire who dresses up like a bat and beats up thugs half to death, which isn't exactly what most sane people would do in his situation. The Joker's specific goals have varied over the years - to drive various people insane, to murder as many people as possible (including the Jason Todd incarnation of Robin - temporarily, at least), or to indiscriminately cause destruction. And that's what makes the Joker Batman's - and, all of comics, apparently - greatest villain: he's unpredictable and unrelenting, with little or no concern for himself, because this is all a joke to him. None of it really matters. While everyone else worries about the gravity of the horrible situations comic books find themselves in, the Joker's in the corner, laughing.
...Except in the Christopher Nolan movies, where he was put in jail and never heard from again.