Another option for the main antagonist could be a group of werewolves who are against Klaus because of his vampire side. They consider him an abomination and when they see him with Landon, they decide to take action. They might believe that Landon is being corrupted by Klaus and want to rescue him while getting rid of Klaus at the same time.
A powerful witch coven might be the main antagonist. They could be jealous of the power that Klaus and Landon possess together. The witches might try to use dark magic to separate them and steal their powers for themselves. Maybe they have a prophecy that says the union of Landon and Klaus will bring about a change in the supernatural power balance that they don't want.
It might start off rocky. Klaus is very protective of Hope, so he could be hostile towards Landon at first. But as time goes on, if Landon shows he's truly good for Hope, Klaus could slowly warm up to him.
Well, perhaps Klaus will initially be skeptical of Landon as Hope's boyfriend. He might test Landon's loyalty and strength. Maybe there'll be some tense moments where Klaus's protective nature for Hope clashes with Landon's attempts to prove himself worthy of her.
One idea could be that Landon, being a unique supernatural being, and Klaus, with his complex vampire - werewolf hybrid nature, form an unlikely alliance to fight a common enemy that threatens both their worlds. Maybe a powerful dark magic user is trying to take over the supernatural realm and they have to combine their skills.
Maybe a rogue ninja who has somehow tapped into dark powers related to Kami's domain. This ninja wants to use these powers to take over the ninja world, and Naruto, with Kami's help, has to stop him. In this fanfiction, the rogue ninja could have some personal vendetta against Kami as well, which adds more depth to the story.
There's a possibility that an evil scientist from another planet could be the main antagonist. This scientist wants to use Bulma's knowledge and Cell's power for his own evil experiments. So he tries to break up their partnership and capture them both for his own purposes. He sends his minions after them and creates various obstacles for Cell and Bulma to overcome.
It might not be so straightforward. While Esdeath has the potential to be the antagonist, there could be other forces at play. For example, there could be a third party that is manipulating both Tatsumi and Esdeath for their own gain. In this case, both Tatsumi and Esdeath could be seen as victims of this greater evil, and they might have to team up against this new threat. However, if we consider the traditional view, Esdeath's actions and beliefs are in direct conflict with Tatsumi's, so she remains the likely antagonist.
Perhaps the main antagonist is an entity that represents chaos and destruction itself. It could be a force that is awakened by the meeting of Mewtwo and Arceus, seeing their combined power as a threat to its existence, and thus tries to stop them from achieving whatever goal they have in the fanfiction.
The main antagonist might be a being from another dimension who is able to manipulate both magic and the Hulk's gamma - irradiated energy. This being wants to use the chaos caused by the meeting of Harry and the Hulk to open a portal to let in more of his kind to take over all the universes. He sets traps for Harry and the Hulk and constantly tries to keep them from working together to stop him.
Perhaps an old enemy of Jiraiya who was thought to be defeated but has now resurfaced. This antagonist targets Boruto to get to Jiraiya, thinking that by harming Boruto, he can draw Jiraiya out and finally get his revenge. He would be a powerful and cunning foe, making it difficult for Jiraiya and Boruto to face him.
Perhaps a rogue group of mermaids and mermen. They don't like the idea of Triton allying with Percy, a half - blood. They believe that Triton should only focus on the pure - blooded sea creatures. So they become the main antagonists, constantly attacking Percy and trying to turn Triton against him.