This is a list of many of Mysterion's minor and major antagonists.
The Coon (also known as Eric Cartman), is one of Mysterion's main antagonists. His motive was that unlike him, Mysterion actually helped people and became more popular among the kids and the police alike. The Coon later devised a plan to make Mysterion unmask himself. With the help of Professor Chaos, he made Mysterion appear at an abandoned hospital by threatening to blow it up. There The Coon "helped" Mysterion by breaking Chaos' nose to silence him on his involvement. The Coon succeeded in making Mysterion not only unmask himself, but also had him put in jail for Vigilantism.
This event started a bitter rivalry in which The Coon was on the losing end. The rivalry seemed to end when Mysterion and The Coon along with many of the kids, founded Coon and Friends, a superhero group dedicated to justice. However, the Coon reverted to his evil ways when the group was upstaged by Captain Hindsight. The Coon's plan was to blackmail Hindsight into joining them using Chaos as a patzy. By taking sex pictures of him dressed as Courtney Love having an affair with Hindsight. While that was going on, BP Oil accidentally unleashed Cthulhu, whom laid waste to the oil site. Rather than help the people in the Gulf, The Coon decided to continue his blackmail plan. This was the final straw for Mysterion, whom was already mad when Mint-Berry Crunch and Mosquito were assaulted by The Coon for trying to take charge. Mysterion and the group kicked him out and kept the name to piss him off.
This prompts The Coon to seek out and form an alliance with Cthulhu, whom only worked with The Coon because he made him think he was a friend. With Cthulhu on his side, Cartman sent Coon and Friends to Oblivion and decided to rid the world of his enemies, the Jewish community, Whole Foods Markets, and Justin Bieber.
Mysterion uses immortality to escape oblivion so he could get help. But the only help he could get was Mint-Berry Crunch, who ran before Cthulhu could send him to Oblivion too. He confronts Cthulhu and Cartman demanding that Cthulhu kill him. He is ignored but it gives enough time for Mint-Berry Crunch's father to unlock Crunch's abilities, defeat Cthulhu and save their friends. The Coon was then thrown in prison with Chaos as punishment for his crimes.
Professor Chaos, the "evil" alter ego of Butters Stotch, was a harmless villain, but nonetheless, he was foiled many times by either The Coon or Mysterion. While he is not afraid to express his hatred on the Coon, he genuinely fears Mysterion. Almost enough to tell him of The Coon's involvement of the hospital scheme had The Coon not intervened. Presumably, for his part of the crime, he is placed in The Coon and Friends jail, where he is eventually joined by The Coon.
Though not intentionally a villain, after Hindsight found out about the blackmail photos, he got drunk and decided to take his anger out on Coon and Friends. Mysterion was brave enough to hold him off. Hindsight was the first to know of Mysterion's immortality before he decided to eliminate his own superpower.
Cult of Cthulhu
The Cult of Cthulhu was a group of people whom worshipped the coming of Cthulhu. Though it seemed heavily implied that many of the members, including Stuart McCormick and Mrs. McCormick, though they were only there for the free beer. Their key members included the unnamed leader, Richard Adler, the Star Trek nerds, and the Goth Kids. The leader was first seen at the Coon and Friends' bake sale to raise money in stopping Cthulhu. He remarked to the group that they will never be able to stop him Mysterion investigated further, even interrogating his mother and father because he realized he may have had a lead on explaining his immortality. Though they couldn't tell him due to their claim of being too drunk to remember, which he believes. He then decides to confront the Goth Kids about information on a poem he overheard during one of their meetings. Before they can answer him, the leader shows up and kills him with the Kindergoth's knife. He comes back and later confronts the Goth Kids, who had quit the cult. They envied him for seeing Oblivion and told him only an immortal can kill an immortal. After Mint-Berry Crunch intervenes, the Cult was never heard from again.
Cthulhu was less of a villain, more so a mindless beast. All he did was send Coon and Friends to Oblivion under Cartman's orders. When Mysterion escaped and confronted Cthulhu, he was ignored by the beast. However, Cthulhu was stalled long enough for Mint-Berry Crunch to send him back to his own dimension.
Jessica Pinkerton was a bully from Greeley who attempted to bully Karen McCormick. Before she could hurt Karen, Mysterion intervened and beat her up. He then told her, along with the rest of the kids, that Karen was "off limits".
The Weatherheads were a strict agnostic family who abused their foster kids when they showed any type of certainty regarding religious events. After the foster children told them about Karen's "guardian angel" (who was, in actuality, Mysterion), the Weatherheads took them to the basement to waterboard them Dr. Pep-er. Mysterion (as Kenny) escaped, donning his outfit once more to save the foster children. He tricked the Weatherheads into drinking a Pabst Blue Ribbon, which later led to their arrest.
While abusing their children was nothing new for Stuart and Carol McCormick. Kenny decided enough was enough when he became Mysterion. It is unknown what he did to them, but it was implied to be enough to terrify them once they've seen him in his costume. Mysterion used that to his advantage to make them treat him and his siblings nicer and give them allowances.