A witch might be the main antagonist. Maybe the witch had a plan that involved Damon as a vampire, and his new human state messes up those plans. So, the witch tries to reverse his humanity or use him in some dark magic spell.
Another human could be the antagonist. This human could be jealous of Damon's past as a vampire and the attention he still gets. So, they try to expose Damon's past misdeeds as a vampire to the new human community he's trying to be a part of, causing him all sorts of trouble.
It could be a vampire who resents Damon for becoming human. This vampire might see it as a betrayal of their kind. They could try to either turn Damon back into a vampire against his will or simply make his human life miserable.
A powerful witch could be the antagonist. She might have been the one who turned Damon human again against his will, and now she has some sinister plan for him. For example, she wants to use his new human form to perform some dark magic ritual that requires a human with a vampire past.
The main antagonist could be a dragon hunter. Since Saphira is now in a human form and has lost her dragon defenses, the hunter sees her as an easy target. He might be after her because he believes that she has some connection to the dragons and he wants to use her to find the dragon lair or something valuable related to dragons.
It could be another ghost who is jealous of Casper's new human form. This ghost might try to sabotage Casper's attempts to fit into the human world, perhaps by causing chaos around him and making humans afraid of him again.
It could be a dark magic user who doesn't want the human - turned - Twilight to succeed. Maybe this antagonist sees the new Twilight as a threat to their own power or plans in the pony world.
A plot could revolve around Damon trying to make amends for his past vampire deeds as a human. He could start by helping the victims of his previous vampire attacks or their families. Also, his love life would change. If he was in a relationship with a vampire or a human before, now as a human, new dynamics would emerge. He might worry about being too weak to protect his loved ones.
It could be an old vampire enemy of Damon's. Maybe someone from his past who has a vendetta against him and sees the baby as a way to get revenge. This antagonist could try to kidnap the baby or cause trouble in their lives.
Another plot could be that Damon becomes human again to be with a human he loves. But once he is human, he realizes that the world he thought he knew as a vampire is very different. He has to start from scratch in building relationships, getting a job, and learning how to live without his vampire powers. He also has to face the jealousy and hatred from some vampires who see his transformation as a betrayal.
Another possible antagonist could be a powerful vampire hunter. He sees Damon as a threat and Elena as a potential target or a way to get to Damon. When Damon and Elena meet, this hunter is already watching them. He plans to use their new relationship against them, making their first meeting the start of a lot of trouble for both of them.
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 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.