It could be an old vampire who sees Elena as a threat to his power or territory. Maybe he doesn't like the idea of a newly - turned vampire causing a stir in the vampire community and decides to take her out.
A witch might be the main antagonist. Since Elena has turned into a vampire, the witch could see her as an abomination and use her magic to try and reverse the transformation or simply destroy her. The witch could also be working with other vampires who have a vendetta against Elena.
It could be a powerful vampire clan that doesn't want Harry, a new vampire, to disrupt their ways. They might try to either kill him or force him to join their ranks against his will. They could see him as an outsider who doesn't belong in the vampire world and a potential danger to their secrecy.
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 powerful sorcerer from the time she travels back to. This sorcerer might sense that Elena doesn't belong in that time and wants to stop her from interfering with his plans. Maybe he has some dark magic he wants to use to take over the kingdom or town she's in.
A powerful and corrupt Pokemon trainer could be the antagonist. This trainer is jealous of the boy's unique transformation into a Pokemon. He wants to use the boy's powers for his own gain, like winning all the Pokemon battles and championships. So, he hunts the boy down, causing all sorts of trouble for him during his journey as a Pokemon.
Maybe Team Rocket could be the main antagonist. They might see Ash's transformation as an opportunity to finally capture Pikachu. Since Ash is in a more vulnerable state as a girl, they could try to use different tactics to take advantage of the situation.
Perhaps a jealous trainer. This trainer has always been envious of Ash's success and now that Ash is in a vulnerable state as a Zorua, the trainer sees an opportunity to get rid of him for good. The trainer could try to use his own Pokémon to capture Ash or even harm him, making the trainer a formidable antagonist in the story.
Perhaps an evil mage who actually intended for the transformation to go wrong on purpose. They might want to use Sans' new female form to cause chaos in the Underground. They could be trying to manipulate Sans into doing bad things or using her to get to other important characters.
Maybe a powerful and envious Mewtwo could be the antagonist. Since Ash has now become a Mew, Mewtwo might feel threatened or think that Ash doesn't deserve such power. So, Mewtwo could try to fight Ash to prove his own superiority.
It could be a new villain who is specifically targeting Gohan because of his new form. This villain might see Gohan's transformation as a sign of weakness or an opportunity to mess with the Z - fighters. Maybe they want to use Gohan's confusion and the chaos it causes among his friends and family to their advantage.
It could be someone who wants to take advantage of Minato's new female form. Maybe a villain who has a vendetta against Minato in his original form and sees this as an opportunity to further humiliate or harm him.