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.
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.
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.
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.
There could also be new antagonists. For example, some of the more traditional wizarding families who are against the idea of a female Harry. They might see her as a threat to the old - fashioned ways of the wizarding world and try to undermine her.
Perhaps it's a jealous ninja from another village. This ninja has always been envious of Naruto's power. So when he gets the chance, he uses a dark magic to turn Naruto into a wolf. His goal is to make Naruto weak and lose his status among the ninja community.
The main antagonist could be an evil knight who has a vendetta against dragons. When the princess turns into a dragon, he sees her as a prime target and tries to slay her, believing all dragons are evil. He doesn't care that the princess was once human and is only focused on his own prejudiced views.