Another possibility is that a group of anti - Sonic forces could be the antagonists. They've always hated Sonic for his interference in their evil plans. When Sonic turns into a girl, they spread false rumors about this new Sonic being an impostor or a dangerous entity. They try to turn Sonic's friends against him and use this chaos to carry out their long - awaited takeover of the world.
Maybe a new character could be the main antagonist. This character could be jealous of Sonic's speed and popularity. So, when Sonic turns into a girl, this antagonist sees it as a chance to frame Sonic for various crimes in this new form. This would make Sonic's friends doubt him and isolate him, all part of the antagonist's plan to take Sonic's place as the hero of their world.
It could be an evil wizard who was the one who actually caused Gumball to turn into a girl in the first place. The wizard has some ulterior motives, like using Gumball's new form to gain power or to cause chaos in the town. He tries to prevent Gumball from finding a way to turn back and keeps creating obstacles for Gumball and her friends.
It could be a villain who is obsessed with creating chaos through strange transformations. This villain might have targeted Deku specifically because of his status as a rising hero. They want to see how Deku will cope with being turned into a girl and use it to undermine his confidence and hero image.
Ganon could still be the main antagonist. Even though Link has turned into a girl, Ganon's goal of taking over Hyrule remains the same. He might underestimate Link in her new form, which could give Link an advantage. For example, Ganon might not expect the girl - Link to be as strong or resourceful as the male Link, but she proves him wrong.
Perhaps a jealous classmate who has always been in Izuku's shadow. Now that Izuku is a girl, this classmate sees an opportunity to undermine her. They spread rumors about how Izuku's transformation is some sort of cheat or that she's not the same reliable person she was as a boy. This classmate's actions and attempts to sabotage Izuku would make them the main antagonist.
It could be a jealous trainer who doesn't like the attention that girl - Ash is getting. This trainer might try to undermine her at every turn during Pokemon battles.
There could be an ancient evil spirit that was released when Aang turned into a girl. This spirit feeds on chaos and the disruption of natural order. It sees Aang's transformation as a sign of the world being out of balance and tries to make it even worse. It might target Aang specifically because he is the Avatar and his new form gives it an opportunity to create more disorder.
Dr. Eggman would be an obvious choice. Since Sonic is now in a more vulnerable human form, Eggman could see this as the perfect opportunity to finally defeat Sonic and take over the world. He might come up with new devious plans, like creating robots specifically designed to target a human Sonic.
Maybe it's a group of purist wizards who form a secret society. They are determined to 'purify' the wizarding world by getting rid of anyone or anything that is not a normal human wizard. Harry, as a monster girl, becomes their prime target. They use dark magic and underhanded tactics to try and capture or kill Harry.
It could also be a new character, perhaps a powerful and evil wizard from a forgotten zone. This wizard could be trying to spread chaos and destruction in the Sonic world, and Antoine stands in his way.
Perhaps an evil mage who actually intended for the transformation to go wrong on purpose. They might want to use Sans' new female form to cause chaos in the Underground. They could be trying to manipulate Sans into doing bad things or using her to get to other important characters.