This list is filled with spoilers so approach with caution. To fully understand the characters I'm describing, you must play the games and experience them first hand. Keep in mind that my favorite villains are based on my opinion. Also note that these are based on the games that I have played. Enjoy.
10) Saren (Mass Effect): From the beginning, Saren is a dick. You instantly hate him and hope for is defeat. But as the story progresses, you understand his true motivation of saving the galaxy from the Reapers, however misguided he was. In the end, he redeems himself by taking his own life to stop Sovereign's control over him. Saren is a 3-Dimensional villain and takes his place on the list.
9) Loghain (Dragon Age: Origins): His betrayal in the beginning of the game creates a deep hatred for him that only his death would satisfy. Even if you decide not to kill him in the end, the wound caused by his betrayal will never go away.
8) Cesare Borgia (Assassin's Creed: Brotherhood): All previous assassinations in the series made you question if killing them was truly the right thing to do. Cesare Borgia is the exception. He is a spoiled brat who will do anything including murdering his own family to get what he wants. Only the throne of Italy would suffice, and even if he succeeded, he would probably want more. You feel no regrets when you throw him from the top of the fortress walls.
7) Letho (The Witcher 2: Assassin's of Kings): Letho is a complex villain. First, he has a history with Geralt. A history that Geralt himself doesnt remember until the end of the game. Second, you have no idea what his true intentions are until the end of the game. Leto is a constant mystery until the lengthy discussion with him in the epilogue. At the beginning, you long await the final duel with Letho, but are hesitant when the option to fight and kill him finally arrives.
6) The Joker (Batman Arkham Asylum, Arkham City, & Arkham Origins): The Joker is absolutely insane. His insanity provides an unpredictable struggle throughout each entry in the series. He is a complex individual that no one, not even the Joker, fully understands. It would be foolish not to include him on my list.
5) Zachary Comstock (Bioshock Infinite): Comstock has a serious God complex issue. He boasts about being a prophet and a servant of God while his actions prove the opposite. He is a asshole who will stop at absolutely nothing to get what he wants. What makes him an even greater antagonist to Booker is that he is Booker from an alternate universe. Comstock became who he is based off one simple decision when he got baptized and reborn while Booker turned away from Baptism. Comstock is an extremely complex character that all began from one decision. As a Christian, it was interesting for me to see a villain who went so far in the extreme that he actually became that which he swore to oppose.
4) Haytham Kenway (Assassin's Creed III): Through out the game, you have no idea how to feel about Haytham. As the father of Connor and the Templar Grandmaster, you really don't know how this is going to end. Haytham tries to be a father to Connor by showing him the "error" of his ways. But when Connor's conviction to the Creed and preservation of freedom, Haytham was willing to do what he thought was necessary to preserve his dream for the future.
3) The Illusive Man (Mass Effect 3): The Illusive Man's a dick. It's as if his sole purpose is to make your life difficult. He is constantly getting in your way to save the galaxy from annihilation to further his impossible goal of controlling the Reapers. He is willing to sacrifice the whole galaxy to get what he wants, to strengthen humanity.
2) Frank Fontaine (Bioshock, & Bioshock Infinite: Burial at Sea Episode 2): Fontaine is a manipulative, lying bastard. Through out Bioshock, he pretends to be an innocent family man named Atlas while he is actually secretly controlling you to further his own goal of ruling Rapture. Once he gets what he wants, he reveals his true colors and attempts to rid himself of his useful pawn that he created. In Burial at Sea, he has very cruel methods of torture to get what he wants. Ultimately, he is nothing more than a terrorist and a atom addict. But since he's smart and clever, that makes him one of the most dangerous people imaginable.
1) Darth Malak (Star Wars: Knights of the Old Republic): You have a score to settle with Malak. In the very first scene with him, he orders the destruction of a whole planet. He ends the lives of billions of people. This sets the tone for Malak throughout the game. Your goal throughout is to defeat Malak, but you don't really feel a reason to on a personal level. That is until your first encounter with Malak and he reveals that you were his master, Darth Revan, and he killed you to take his place as the Dark Lord of the Sith. At least, that's what he thought. You are not ready to face Malak in that first encounter. In the end, you escape but he captures Bastila, a very important jedi and your love interest. Now, it becomes very personal. After finishing your lengthy journey to find the Star Forge, you find that Malak has turned Bastila to the Dark Side. After an emotional duel, you either kill Bastila or you turn back to the light. Either way, you feel more determined to defeat Malak than ever before. When you finally reach the final confrontation, you feel goose bumps in anticipation for this epic duel. And what an epic duel it is. When you finally defeat Malak, he realizes the mistakes of his life and the folly of his belief of being invincible. Rather than feeling happy for his defeat, you can't help but feel pity for Malak.