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.
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.
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 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 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.
It could be a character who wants to use Percy - turned - Aku for their own evil purposes. Maybe a dark wizard who thinks that Aku - Percy can be the ultimate weapon to take over the world. This wizard would try to manipulate Percy's new form and powers to do his bidding.
Perhaps a powerful vampire lord who sees Sookie as a threat to his power. Since she was once human and has connections to both worlds, he might fear that she could rally other vampires and humans against him. He could try to eliminate her by any means necessary, leading to a lot of action - packed scenes in the fanfiction.
It could be Sasuke. If Sasuke has turned completely to the dark side and Naruto fails to save him, Naruto might be so frustrated and angry that it starts to make him cold - hearted towards everyone. Sasuke's actions could be the trigger for Naruto's transformation.
The Ministry of Magic could be the main antagonist. They might view Harry's fascination with Dementors as a sign of him turning to the dark side. So they try to stop him from his research and exploration of Dementors, fearing he'll use their powers for evil. After all, Dementors are associated with dark magic in the eyes of the Ministry.