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.
It could be a corrupted version of one of Sonic's friends. Maybe Tails gets possessed by an evil spirit. In Sonic's human form, he has a harder time fighting against this once - friendly foe. The possessed Tails could use his knowledge of Sonic's strengths and weaknesses to create elaborate traps and attacks, making him a formidable antagonist in the fanfiction.
A new villain could be introduced. For example, an evil scientist from another dimension who is jealous of Sonic's speed and power. When Sonic turns into a human, this villain could try to steal Sonic's remaining powers or use him as an experiment to find a way to transfer super - speed to himself. This would make the new villain a major threat not only to Sonic but also to Sonic's friends and the world they live in.
It could be another monster who is jealous of Sans' new form. This monster might feel that Sans is getting special treatment or opportunities because he's now a human. So, this jealous monster tries to find a way to either turn Sans back into a skeleton against his will or make his human life miserable by causing trouble for him in the human world, like spreading false rumors about him.
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.
Perhaps there could be a jealous teacher in the school where he starts working as a human. This teacher is threatened by Koro Sensei's popularity among students, even though he's now human. So, this teacher starts to spread rumors or create problems for him to get him fired.
It could be another monster who is jealous of Sans getting all this new - found attention as he turns into a human. This monster might try to stop the transformation process or make Sans' life difficult in his new human form.
One possible plot could be Sonic accidentally getting hit by a strange energy beam during a battle with Dr. Eggman. This beam could have some sort of mutagenic effect that slowly starts to transform him into a human. As he turns into a human, he has to deal with the loss of his super speed at first. He then has to adapt to living as a human while still trying to protect his friends and the world from Eggman's new threats.
Obviously, Sonic himself would be a main character, even in his baby form. His friends like Tails, Knuckles, and Amy would also be main characters. Tails could be the one trying to figure out how to turn Sonic back. Knuckles could be the protector, and Amy could be the caretaker.
A powerful and corrupt Pokemon trainer could be the antagonist. This trainer is jealous of the boy's unique transformation into a Pokemon. He wants to use the boy's powers for his own gain, like winning all the Pokemon battles and championships. So, he hunts the boy down, causing all sorts of trouble for him during his journey as a Pokemon.
Maybe Team Rocket could be the main antagonist. They might see Ash's transformation as an opportunity to finally capture Pikachu. Since Ash is in a more vulnerable state as a girl, they could try to use different tactics to take advantage of the situation.
Perhaps a jealous trainer. This trainer has always been envious of Ash's success and now that Ash is in a vulnerable state as a Zorua, the trainer sees an opportunity to get rid of him for good. The trainer could try to use his own Pokémon to capture Ash or even harm him, making the trainer a formidable antagonist in the story.
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.