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 be a new character created specifically for the fanfiction. Maybe an alien race that has a vendetta against both the Saiyans and Earthlings and sees the union (even if it's just a meeting) between King Vegeta and Bulma as a sign to start a conflict.
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.
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.
If the fanfiction is set in Columbia from Bioshock Infinite, Comstock would likely be the main antagonist. His fanatical religious beliefs and his plans for Columbia would clash with Kagome. Comstock wants to maintain his power and carry out his dark plans, and Kagome's presence, with her different way of thinking and her powers, would disrupt his carefully laid - out schemes.
It could be the Red Queen. She might see Alice's presence in Mirana's world as a threat to her own power and try to stop their friendship.
Perhaps a rogue Overwatch agent who has turned against the organization. When Harry arrives, this agent sees an opportunity. He believes that by using Harry's magic, he can take over Overwatch and rule the world. So he tries to manipulate Harry and turn him against Tracer and the rest of the good - hearted Overwatch members.