Perhaps it could be a group of bullies from Issei's school days. They used to pick on him and now he's coming back to make them pay.
In this fanfiction, the antagonists might be other characters who are jealous of Issei's potential or abilities. They try to sabotage him at every turn, and in the end, Issei decides to take revenge on them for all the harm they've caused him and his future prospects.
Well, it could be about Issei seeking revenge on those who wronged him in the past. Maybe someone bullied him or betrayed his trust, and now he's out for payback. He might use his unique skills or powers to get even.
It could be some hidden members of Naruto's family itself. Maybe there are relatives who have been manipulating things from the shadows and their actions led Naruto to believe he needs to take revenge on the family as a whole.
Maybe the hidden organizations within Konoha that work in the shadows. They could have been involved in some plot against Naruto that led to his decision for revenge. They would be the ones trying to stop Naruto from exposing their secrets and exacting his revenge on the village as a whole.
Other vampires might be his main antagonists. They could see Issei as a threat, perhaps because he's a new vampire with different ideas or powers. Or they might want to use him for their own gain.
It could be an old enemy of the group who has a personal vendetta against Issei. This antagonist might be jealous of Issei's power or popularity within the group and plots to turn everyone against him. They could spread false rumors or create false evidence to make it seem like Issei has betrayed the group.
A group of vampire hunters could also be the antagonists. They might not be able to tell the difference between Issei and a full - blooded vampire and target him. They could be very zealous in their mission to wipe out all vampires and view Issei as just another one to be hunted down.
It could be any fan who is interested in creating a story around Issei's downfall. There are many amateur writers in the fanfiction community who might come up with such a concept.
It could be the Ministry of Magic. They have often been shown to be corrupt and self - serving in the original series. If they try to manipulate Harry again, he might see them as the main antagonists and target them in his revenge.
It could be a new group of rogue shinobi who have been causing chaos in the ninja world while Naruto was away. They might have targeted Naruto's friends or family, which is why he's back for revenge.
It could be a rogue group of Shinra scientists. They might be obsessed with power and see Cloud as the perfect subject for their unethical experiments. They don't care about the consequences for Cloud or the world at large, just their own thirst for knowledge and power.