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.
There could be a group of rogue ninjas who want to steal the secrets of the Uzumaki and Jiraiya's techniques. They become the main antagonists as they constantly try to attack Boruto and Jiraiya, and prevent them from passing on or developing new jutsu.
It could be a rogue ninja from a forgotten clan who has a vendetta against the Uzumaki. This antagonist might see Shinachiku as a threat because of his potential power and decides to target him and Boruto to stop them from achieving something great in the Hidden Leaf Village.
Jiraiya could act as a mentor to Boruto. He might correct Boruto's mistakes in combat or give him advice on how to handle difficult situations. Boruto would listen intently, trying to soak up all the knowledge from this legendary ninja. And they could also have some light - hearted moments, like joking about Naruto's clumsy moments when he was young.
Maybe in the fanfiction, Jiraiya is summoned by a new jutsu gone wrong. When he meets Boruto, he mistakes him for Naruto at first. As they interact, Jiraiya realizes Boruto's own unique struggles. He shares his wisdom about handling the expectations that come with being a ninja from a famous family, and Boruto learns a great deal from him.
In this fanfiction, Boruto might learn some unique ninja techniques from Jiraiya. Jiraiya could see the potential in Boruto and train him in his own unorthodox ways. Maybe Boruto would be introduced to Jiraiya's toad summoning, which could add a whole new dimension to his combat abilities.
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 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.