A new group of rogue ninjas who have a vendetta against the Jinchuuriki for some past event. They could believe that the Jinchuuriki are a threat to the balance of the ninja world and decide to take matters into their own hands by eliminating Naruto and his Jinchuuriki family. This group could be made up of former prisoners who were affected by the power of the tailed beasts in some way and now seek revenge.
It could be Orochimaru. He has always been interested in power and the secrets of the tailed beasts. So, he might see Naruto and the Jinchuuriki family as a source of great power to experiment on or steal from.
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.
The elders of his family or clan could be the main antagonists. They might have exiled Naruto in the first place due to some old - fashioned beliefs or fear of his power. Throughout the fanfiction, they could try to stop Naruto from finding out the truth or coming back to the clan.
His family members themselves could potentially be antagonists in a sense. If Naruto is rejecting them, there could be some family members who try to stop him from leaving or try to change his mind forcefully. They might see his rejection as a threat to the family's reputation or unity.
In this fanfiction, the plot could revolve around Naruto and the Jinchuuriki family being hunted by a powerful organization. They are forced to go on the run and hide in different parts of the ninja world. During this time, Naruto discovers more about their shared heritage as Jinchuuriki. They also have to deal with the internal struggles of some Jinchuuriki who are not fully accepting of their role, and Naruto has to use his leadership skills to keep them together and safe.
It could be Orochimaru. Even though he was defeated before, he might come back with a new plan. Maybe he wants to use Naruto and Naruko's family for some dark experiment, like trying to extract the unique chakra combination that their family might have.
One possibility is a group of shinobi from a rival village. They believe that Naruto's mother held the key to some great power or secret that could give their village an edge. So, they try to either capture Naruto to extract the information or stop him from uncovering more about his mother. Another could be a dark spirit that was somehow sealed away by Naruto's mother long ago, and now it's trying to break free and take revenge on her through Naruto.
Maybe Danzo. He's always been a power - hungry character. In a story where Naruto doesn't have the jinchuuriki advantage, Danzo could see it as an opportunity to take over the village without the threat of Naruto's special power standing in his way.
Another possibility is that there could be a new character introduced in the fanfiction, a mastermind who manipulates Harry into believing that his family is a threat. This new character could be the main antagonist.
Perhaps a rogue ninja group that has a vendetta against Anko. When she forms this new family with Naruto, they target the whole family unit to get back at her. They might see Naruto as a way to get to Anko or vice versa, and constantly attack and create chaos for them.
It could be his own family members who abandoned him. They might come back as antagonists, trying to stop Naruto from reaching his full potential or causing trouble for him out of envy or regret. Maybe they have joined a dark force and are now working against him.