Villainsvillainsvillainsvillains--ahem. Warning. Fan ranting ahead.
1. Gabriel Gray/Sylar (Heroes)
This dude . . . is just awesome, yo. When he was first introduced in season one, all we were shown were the gruesome and physics-defying results of his murder scenes. We never even saw him closely for the entire first half of the season--he was just a figure in shadows, throwing stuff and people through the air with a flick of his hand. When we finally did meet him, he had a creepy, intense stare and a slightly gravelly, creepy voice. Zachary Quinto used these to great effect and combined them with an obsessive, disturbing curiosity in his performance to drive home the hunger that lay behind Sylar's character: He wants to see how you work, and he's going to open you up and examine your parts like a clock to do it. he also had a really awesome theme song background sound effect of ticking clocks to underline the twisted function of his mind. Sylar is very much the driving force of season one's plot, to the point where he essentially hijacks another plot to turn himself into the final challenge for the protagonists at the end of the season.
Heroes suffered from a good deal of shoddy writing, and in later seasons began irritatingly waffling back and forth between flirting with redemption and going back to being stone-cold insane and evil. But despite all of that, he still stayed awesome. He frequently beat the snot out of the villains of future plot lines, as if to remind the universe how awesome he was. He's both smart and insane, manipulative and brutally forceful, and is pretty much the best character on the whole show.
2. Human!Yawgmoth (Magic: the Gathering)
Yawgmoth spent most of his character career as the unseen lord of Phyrexia, a land of organisms composed partly of machinery and partly of undying flesh. The Phyrexian armies were entirely devoted to Yawgmoth, and single-mindedly carried out his plans to spread glorious machine compleation (not a typo) throughout the entire multiverse. When Yawgmoth finally appeared on screen, he was revealed to be a sapient black cloud of death, swiftly flowing across the plane of Dominaria to choke out all the imperfect life and fold it into himself.
None of that makes Yawgmoth particularly terrifying; it's pretty par for the course with dark lords in fantasy settings. Yawgmoth is terrifying because of his behavior as an ostensibly normal human during the prequel novel The Thran. Yawgmoth's behavior as just as monstrous as a human as he would later be as a monster--but it's all the more terrifying because he is presented as just a regular human with some very, very sick ideas. After being attacked by a bear and receiving an injured arm, the mage who heals him has to chide him for poking around the wound and infecting it. He responds by saying that he couldn't pass up the opportunity to study human body parts. Already, he was looking at living things as parts. (An older version of the story, which I believe is unfortunately no longer canon, had him remove sinews and tendons from the bear's arm to replace his injured ones.) Yawgmoth is all about upgrades, you see; when he learns about the existence of planeswalkers (super-wizards who don't age), he captures one and has some of minions peel open her body one cubic meter at a time looking for the one special thing that made her different, so that Yawgmoth could insert it into himself and become more powerful. One line summarizes Yawgmoth's entire character: after months of striving to fight a plague (which it's heavily implied that he created and spread in the first place), he felt that the people he had helped weren't acting respectfully enough. When the leader of those people chided him for his ego, saying that Yawgmoth was a healer, not a god, Yawgmoth replied, "After everything I have done for these people? They had damn well better treat me as a god."
Yawgmoth was an ordinary man who believed he deserved godhood--and he made it happen.
I'm going to get major flack for this one, but
3. Professor James Moriarty (The Final Problem
Yeah, I know, it's Moriarty, but bare with me. Most of what you think about Moriarty comes from later adaptions of Holmes stories, like Sherlock or even The League of Extraordinary Gentlemen. But the original Moriarty? Is basically a non-entity when seen through the lens of the entire, original Doyle canon. If I may be uncharacteristically crude, Moriarty was basically an asspull of Doyle's part as part of his attempt to kill off Holmes and move on to other writings (which I'm not criticizing; it was his right to do so). Moriarty is thrown into the story just to be killed off and take Holmes with him. He is shown to have high intellect, like Holmes, and good fighting skills and strength, like Holmes. But because he never shows up in any other story, all that info basically just rings false; it's too much "tell, don't show" and it makes for a rather impotent and forgettable villain (again, looking only at the original canon which is all that exists).
4. Seymour Guado (Final Fantasy X)
This is an opinion that I've only developed recently. Back in high school, all my FF fan friends and I hated Seymour (and I'm embarrassed to admit, a lot of that was childish, group-of-males reaction of, "Ew, he's so effeminate, why doesn't he put on a shirt and also speak several octaves lower). Recently, though, I've thought about his goals and motives more, and I find myself a lot more understanding of his position.
The setting of FFX in a nutshell is: "A giant whale pops out of the ocean and obliterates entire cities, but sometimes a special summoner goes and beats the whale up and makes it leave us alone for two or three decades." What the majority of the populace doesn't know is that every time that happens, the summoner is sacrificing someone they love, which then becomes the new whale. The original summoner, who started that whole summoner religion, was using the sacrifices and their giant whale body-thing-whatever as a protecive vessel, using the people's reverence for himself to keep himself alive forever, and using what everyone thought was salvation and safety to perpetuate their destruction.
Seymour was a summoner, and sacrificed his mom to fight the whale--except he never tried to fight it. Instead, he looked at the endless cycle of death and temporary peace in his world, and he saw only one hope, one way to end the suffering: kill everyone in the world. With everyone on Spira gone and unable to worship, the whale and the original summoner would die, too, finally ending the cycle. To do this, Seymour saw that he had to sacrifice himself to another summoner to become their summon, allowing him to take control of the whale and obliterate the world and everyone in it. It's absolutely insane, and he committed at least a few murders along the way, including his own father (and one near-genocide!), but in a world where the greatest hope is, "maybe this most recent human sacrifice will get us three whole decades before the giant whale inevitably rises out of the sea and destroys entire cities again!" Seymour sought escape and piece for everyone. And while that wasn't the only way (the player party obviously fixes everything in the end), Seymour lived in a society almost completely dominated by the rhetoric of their faith, and it's hard to blame him for being unable to see beyond what he had taken for granted since he was a child.
He still has an annoying voice, though.
Well, not as annoying as Tidus's.