It could be a powerful demon. This demon has a vendetta against dragons and when he hears about Saphira becoming human, he decides to target her. He thinks that by destroying her in her human form, he can send a message to all dragons. He uses his dark magic to create all sorts of problems for Saphira, from causing nightmares to trying to possess the people around her to turn them against her.
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.
Maybe an envious sorcerer could be the main antagonist. He sees Saphira's transformation into a human as an opportunity to steal her dragon powers that are somehow still latent within her human form. He tries to manipulate her and the people around her to get what he wants. He sets up various traps and illusions to deceive Saphira and her new human friends, causing chaos and danger in her new human life.
One possible plot could be that Saphira, through some magical or scientific accident, is transformed into a human. She then has to learn how to navigate the human world. She might struggle with basic human functions like eating with utensils or wearing proper clothes. At the same time, she tries to find a way to turn back into her original form, all while forming unexpected friendships with humans who are intrigued by her strange behavior and origin.
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 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.
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 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.
Galbatorix could still be a main antagonist even in a time - travel scenario. If they travel back in time, he could be younger and more powerful in different ways. Maybe they accidentally give him knowledge that makes him even more of a threat earlier in history.
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.