It could be an old - fashioned vampire who doesn't like the idea of hybrids and sees Caroline as an abomination.
Maybe a powerful witch who is jealous of Caroline's new powers as a hybrid and wants to take them away from her. The witch could be causing all sorts of problems for Caroline, like casting spells to make her lose control of her hybrid side.
A group of werewolves might be the main antagonists. They think that Caroline becoming a hybrid is against the natural order and they are determined to stop her at all costs. They might hunt her down and try to kill her, believing that it's for the greater good of their species.
Well, perhaps Caroline gets bitten by a werewolf and then turned into a vampire later, thus becoming a hybrid. Maybe she struggles with her new powers and the cravings that come with being a hybrid.
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.
Maybe the Ministry of Magic could be the main antagonist. If Harry turns into a hybrid, the Ministry might see him as a dangerous abomination. They could try to capture him and keep him locked away, thinking that his new form is a threat to the wizarding world's order. They might not understand that Harry is still the same person inside and that his new form could actually be an asset in the fight against evil.
It could be a powerful vampire lord who sees the hybrid as an abomination and wants to destroy them. This vampire lord might view the mixing of werewolf and vampire blood as a threat to the purity of the vampire race.
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 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.
It could be an old and powerful vampire who sees Hermione as a threat to his rule. Since Hermione is a very intelligent witch - now vampire - she might be able to figure out a way to undermine his power.