"The ultimate villain of the story, who's causing the problem the heroes must solve."
Note that Big Bad is not a catch-all trope for the biggest and ugliest villain of any given story. The Big Bad is the one who turns out to be behind several other seemingly independent threats.
The unseen supervillain Nimbus seems to be behind everything. The superweapons at Halloween, the deviser drug used on Merry and maybe also G-Force, and so on. Even some of the Christmas holiday adventures had Nimbus lurking somewhere behind the scenes. We still don't know what he's up to.
That said, "Señor X" seems to be responsible for everything that Nimbus isn't. Among other things, he's indirectly responsible for everything Hecate did, and by connection, half the bad stuff the Alphas were up to early on. More importantly though, a recent story revealed that There was a very powerful and very subtle spell active on campus designed to increase tension and conflict, and he's implied to be the one responsible — making him indirectly responsible for the actions of more or less every on-campus bad-guy to date. Oh and it's practically been confirmed by this point that he's masquerading as a student.
In the recent story "Razzle Dazzle", Thomas Townsend, alias Mephisto the Mentalist, alias Cerebrex the Super-Brain, claims to have been scheming against many different heros for over eighty years. Under the alias Dominus, he's the current boss of the Syndicate. Of course, we don't know for such how much of this is true, since Thomas Townsend admits that he's an Unreliable Narrator.
Considering how little we know about these Whateley Big Bads, it's possible that two or more of them are the same person.
The Blood Gulch Chronicles, spanning the first five seasons, has a rogue Artificial Intelligence known as the Omega (calls itself O'Malley), possessing the minds of several characters and amplifying their negative personality traits ten-fold, most notably Doc. A Faux Affably Evil parody of the Big Bad archetype, O'Malley has aspirations toward omnicide, but is far too hammy to be taken that seriously... until the first episode of the sixth season details his unnervingencounter with another band of Blue and Red soldiers, and it's revealed that he ruthlessly tortured a fellow A.I. out of spite.
Afterward, Reconstruction, the sixth season, has the Meta, a former Freelancer agent with goals to obtain armor enhancements and artificial intelligence to increase his power, mainly due to how progressively insane his mental state developed into from stealing all of those A.I. A weakened Meta returns in Recreation, chasing down and trying to kill Donut, Lopez and Simmons in their new base of Valhalla, having allied with Washington by the end of its last episode. Meanwhile, another Freelancer agent named C.T. was sent to dig up a superweapon on the desert-like Sandtrap. C.T. and his mercenaries killed off the original excavation team and took over the operation, but was delayed by Tucker's timely intervention, even more so once Sarge, Grif, Caboose and Church were brought into the fray. In the eighth season, Revelation has Washington and the Meta as the resident Big Bad Duumvirate, until the Meta turns on Washington by the end.
Michelle Clore from KateModern is responsible, either directly or indirectly, for nearly everything that goes wrong over the course of the series.
Danya commands the terrorist organization in charge of Survival of the Fittest, and is therefore primarily responsible for the students being abducted and forced to kill one another, even though as of yet it is unknown if he has ever directly killed anyone. This makes his status as Big Bad inarguable. At least until he's killed by Dorian Pello.
Each Survival of the Fittest Endgame tends to have one major villain from the students too. V1 had Cody Jenson, the killer of Adam Dodd's girlfriend and best friend, V2 had Mariavel Varella, the biggest killer on the island, who further cemented her status when she killed Bryan Calvert's girlfriend, and V3 had J.R. Rizzolo, who actually ended up winning.
Madness Combat had the Sheriff as its first Big Bad, who got killed relatively quickly, followed by Jebus and eventually the Clown. Then the Auditor showed up and things really hit the fan.
The Emperor, leader of TAROT, has his fingers in nearly every criminal enterprise on Earth in the Global Guardians PBEM Universe. Of course, he's also got his fingers in nearly every major legitimate business enterprise on Earth as well. But then, what do you expect of a villain who is secretly an immortal Niccolo Machiavelli?
The Mysterious Somebody, Bracket Fungus and League of Mary-Sue Factories take this role for the Protectors of the Plot Continuum. Despite being long dead, the Mysterious Somebody could be said to be the most influential Big Bad, as his actions more or less shaped the PPC's identity in-story; the League is a series of offshoots from his original Mary-Sue Factory, and the organisation of the PPC itself is a reaction to his actions as its head.
Both Mechakara and Lord Vyce were bounced from an apparent Big Bad role in Atop the Fourth Wall, with the former being revealed to be working for the latter, and the latter being revealed as the massively outclassed nemesis of the mysterious Entity.
A Game Of Gods originally had Omega as the Big Bad, who was behind all the disappearing Champions and was possessing a doomsday device. However, after he kicked the bucket, Lambda came in and some Fridge Horror came up, resulting in them going back for Echidna and confronting the true Big Bad, Digamma.
In Greek Ninja, it turns out that the no-match-for-any-human-being force that was so strong it could destroy the whole world, was in fact nothing more than a bitter human being himself, who was purposelly reincarnated simply to get revenge and restore the reign of the Olympians.
Taco Man, in "Taco Man: The Game Master," has certain villians. In "Taco Man Plays A Video Game," however, when he got tired of playing Bubsy, Taco Man had a dream of a evil Bubsy forcing Taco Man to play Bubsy 3D, and then, Taco Man realized it wasn't a dream, because the Bubsy 3D title screen was on Taco Man's TV, and the evil Bubsy forced Taco Man to play Bubsy 3D, and then, after Taco Man was treated to a death animation in Bubsy 3D, the evil Bubsy said that there was Bubsy II and Bubsy for the Jaugar, and the evil Bubsy disappears.
