The main antagonist could be an ancient evil that was sealed away long ago. The legend said that only the combined power of the Uzumaki twins (Naruto and his sister) could break the seal. So this evil entity tries to prevent them from realizing their true potential and uniting. It uses mind - control and illusions on the people around them to make their lives difficult and keep them apart.
It could be someone who doesn't want Naruto and his sister to unite. Maybe a rogue ninja who fears their combined power. He might try to drive a wedge between them by spreading false rumors or causing misunderstandings.
Perhaps the main antagonist could be a powerful shinobi from another village who sees Naruto and his sister as a threat to their own village's dominance. This antagonist would constantly try to undermine their relationship and stop them from getting stronger together. They could send assassins after them or try to frame them for crimes in the ninja world.
It could be someone who is jealous of their new - found bond. Maybe a rival of Uzumaki who doesn't want him to have such a powerful ally in his sister.
It could be Frieza. Since Frieza has a history of hating the Saiyans, he might see Goku's sister as a new threat and try to eliminate her.
In a 'naruto meets his twin sister fanfiction', perhaps his sister has been living in a different village all this time. When they meet, she could be a very powerful ninja in her own right. Their meeting could stir up a lot of emotions, like Naruto feeling a sense of family he's never had before. They might team up to face a common enemy, using their shared bloodline abilities in unique ways.
It could be a member of Naruto's family who is fueling the neglect. Maybe an older relative who believes that the sister has more potential or is more worthy of attention and resources. This person could actively try to keep Naruto down.
It could be an ancient monster that has a grudge against the family of Poseidon. Since Percy and his twin are children of Poseidon, this monster might target them specifically. Maybe it's a sea serpent that was once defeated by Poseidon and now wants revenge by going after his descendants.
One possible main antagonist could be a powerful ghost who sees the combination of Danny and his twin sister's powers as a threat. This ghost could be trying to split them up or turn them against each other so that they can't use their powers together to stop his evil plans. Maybe he has some connection to their family's past in the Ghost Zone that makes him particularly interested in them.
It could be a jealous ninja in the village. This person might see Naruto's sister as an easy target since Naruto is often preoccupied. They could spread rumors about her or try to make her life difficult at the ninja academy, taking advantage of Naruto's absence.
Voldemort could be the main antagonist. He might have seen the potential in Harry's twin and decided to get rid of the twin to weaken Harry or use the twin for his own dark purposes.
Maybe a powerful rogue ninja who has discovered a way to steal the powers of divine entities. He sets his sights on Amaterasu and Naruto because he knows that if he can combine their powers, he will be unstoppable. He creates various traps and illusions to separate them and weaken them so that he can carry out his evil plan.
It could be someone who wants to steal Samehada for its power. Maybe a rogue ninja who has heard of Samehada's ability to absorb chakra and plans to use it to take over the ninja world.