[En Sabah Nerd]

Personally I have a few:
Apocalypse- there's something truly tragic about what made En Sabah Nur into Apocalypse, his people and adoptive father were all killed because of what he would become and in doing so created him anyway. He is a product of the fear and violence that tormented his youth, humanity has only itself to blame for one of the Marvel universe's greatest threats. I like Apocalypse so much that my user-name here is a play on his real name.
Kang- the unrivaled master of time travel. Kang is neat because he started as a hero and was turned into Kang from tragedy (Iron Lad with the Young Avengers, and then the Children's Crusade wrecks him emotionally). He becomes cruel, cold, and calculating. Nobody is sacred to Kang, save himself, and he'll kill his own son without much hesitation to secure his own power. His schemes are the most thought out and often the most cunning. His only weakness is his sense of honor, otherwise he'd kill all who oppose him while they're still in diapers, but his honor keeps him in line.
Thanos- much more the typical "I'm evil and hate everyone, kill everything, grarr!" However very few reach the pizaz and level of Thanos. The execution of Thanos, especially from Jim Starlin, is always entertaining and universally dangerous. Plus Starlin plays him so well off of Warlock and their relationship.
Dr Doom- if A for effort goes to anybody, it's Victor Von Doom. This guy like never wins, his plans don't usually even play out for his own benefit. He's definitely dangerous, but even more so he's proud and obnoxious. He does have a sad back-story with his mother, but then again most of Doom's suffering is his own fault.
Green Goblin- arguably the most successful villain in regards to his specific hero. Even more than the Joker is to Batman. He killed Spider-Man's love, ruined his friendship with Harry, and constantly plagues Peter's life. Nobody brings grief to their hero quite like Norman Osborn. Then there was that whole HAMMER take-over deal too.
Honorable mention: Magneto- not always the villain, but when he is he's the easiest to understand why he jumps to violence before reason.