It sounds to me like there are quite a few. I don't know why anyone would ask this question when Bloody Mary from the Wolf Among Us is still fresh in our minds. The main antagonist from Gears of War was female, as was the main antagonist from Uncharted 3, Bioshock 2, The Last of Us (sort of), Persona 4, the third Phoenix Wright game and Dragon Age 2. GLaDOS and SHODAN are clearly feminine despite being technically genderless, and on that note you could even count the Administrator from TF2 as an antagonist.
Much like with female player characters, there isn't really a shortage, so much as there's an imbalance of male and female villains. I don't think it helps when people have to add qualifiers to these things though, like whether or not they're conventionally attractive, whether or not they reform, or whether or not they're the main antagonist. Either they're female or they aren't.