1) AngelusBuffy rarely broke a sweat while slaying vamps, but Angelus was no normal bloodsucker. He was one of history's baddest and toughest vamps, and he was also the evil and soulless version of Buffy's one true love, Angel. Angelus took over Angel's body in season two of Buffy, after Angel found true happiness (while making love to the slayer) and lost his soul due to a gypsy curse.
He earned his reputation as a cruel and sadistic evildoer by tormenting his enemies psychologically as well as physically. He would often hurt or kill his enemy's loved ones just to watch their spirit break. He was gone for a while after the Scoobies restored Angel's soul at the end of season two, but Angelus returned later in Whedon's Buffy spinoff, Angel.
Runners up: And here are the Whedon baddies who just missed the list, mostly because they only showed up for a few eps or didn't dominate a season: Evil Willow, The Gentlemen and Drusilla from Buffy; Lilah, Darla and Holtz from Angel; Badger, Jubal Early and Saffron from Firefly.
2) SpikeThe bleach blonde vamp and his gal pal Drusilla rode into Sunnydale during Buffy's second season. Spike, aka "William The Bloody," was a wicked and merciless devil with a trail of dead slayers behind him. He proved to be a formidable foe for Buffy ... until he fell in love with her and was left unable to harm humans, courtesy of an experiment conducted by the U.S. government.
After becoming impotent, Spike lost his edge for a while and became a sort of comic relief character, a vampire Huggy Bear. After fighting to regain his human soul, Spike became a reluctant champion who helped Buffy and crew save the world, once again, in the series' final episode. Spike later showed up on Angel to fight against the evil senior partners of Wolfram & Hart.
3) Richard Wilkins, aka "The Mayor" The big bad from Buffy's third season was like an evil version of The Middleman: a seemingly non-threatening, polite and often corny chap with a smokin' hot babe for a sidekick. As the mayor of the Scooby gang's hometown of Sunnydale, Wilkins offered a handshake and a smile to every constituent, but he was hiding a whole lotta bad behind that toothy grin. The Mayor turned out to be a skilled sorcerer who made a pact with the Hellmouth demons to live forever in the form of a nasty, pure-breed demon-monster snake thing. Buffy and crew obliterated The Mayor with a library full of dynamite. His last words: "Well, gosh."
4) Lindsey McDonald The "tiny Texan" had no evil supernatural powers to speak of, but hate and blind ambition were enough to turn him to the dark side. As a representative of Wolfram & Hart, Lindsey often clashed with Angel during the show's first two seasons. Despite trying to kill each other several times, Lindsey and Angel sometimes worked together. In the end, Angel recruited Lindsey to help him defeat their common enemy, Wolfram & Hart. But Angel knew he couldn't trust Lindsey, and he ordered the normally peaceful Loren to assassinate him. Lindsey went out stunned that he was killed by one of Angel's "flunkies" instead of Angel himself.
5) Depression The Trio were an annoying thorn in Buffy's side, but they were nothing compared to this big bad. The Scoobies raised Buffy from dead, but the slayer returned aimless and indifferent. It was revealed later that Buffy's soul was ripped away from Heaven, not the hell dimension in which her friends thought she was trapped. Buffy's bout with depression lasted for most of season six. It led to her affair with Spike and created distance between her and sister Dawn. Buffy even sang the blues during season six...
6) The TrioInstead of just one big bad, Buffy's season six had three wannabe big bads who lived to annoy the Scoobies. But as the season progressed, the geeky trio of Jonathan, Andrew and Warren became more dangerous thanks to Warren's thirst for power. The Trio were a hilarious addition to the show, often commenting on Buffy's adventures as if they were watching them on TV and dropping a million geek culture references a minute.
7) The MasterBuffy's first TV big bad is probably one of the most traditional villains in the Whedonverse. The Master was a powerful and ancient vampire with a monstrous face who tried to take over Sunnydale in Buffy's first season. Trapped underground, he manipulated Buffy with hypnotic powers in an attempt to help him escape and open the Hellmouth. The Master actually succeeded in killing Buffy, but she got better and defeated him in combat.
8) Wolfram & HartAnother giant evil corporate-like entity, Wolfram & Hart was at the center of most of the bad mojo seen throughout the entire run of Angel. The inter-dimensional law firm had massive influence on Earth and the demon underworld, influencing the lives of humans and supernatural beings to carry out the will of its demonic senior partners.
9) The AlliancePerhaps Whedon would have introduced a more traditional big bad on Firefly if the show had lasted longer. But this authoritarian government caused enough trouble for Captain Mal and company without having a clearly defined figurehead. The Serenity crew managed to win a few scuffs with this oppressive force, even though they were outmanned and outgunned at every turn.
10) Gloria/ GlorificusAn evil, egotistical and mentally unstable goddess with unlimited power, Glory proved to be one of Buffy's toughest foes. The tall blonde knocked the Slayer on her teeth more than once during Buffy's season five, but her presence on Earth led to the creation of Buffy's sister, Dawn. Glory tried to kill Dawn in order to return to her home dimension, but Buffy sacrificed herself to save her sister and the rest of humanity.