Perhaps Kaguya Otsutsuki is resurrected again, but this time with a stronger will and more dangerous plans. Since Naruto was the one who played a major role in defeating her before, she targets him first in this fanfiction.
Maybe a new, powerful and evil ninja from another land. This ninja could have come to the village and caused a lot of chaos, making Naruto believe that no one in his village was capable of protecting themselves or him. So he blames everyone for their weakness and starts to hate them all, with this new ninja being the root of the problem.
It could be a corrupt ninja from another village who wants to get rid of Naruto as he sees him as a threat to his own plans. This ninja could have framed Naruto to send him to prison.
Another possibility is that there is no single main antagonist. It could be a combination of misunderstandings, village politics, and personal issues within Kurenai herself that lead to her betraying Naruto. For instance, the village elders might be pressuring Kurenai to keep Naruto in check, and at the same time, Kurenai has her own doubts about Naruto's power which could be misconstrued as a reason to betray him.
It could be one of the harem members who has a hidden dark side. Maybe she's jealous of Naruto's closeness to others in the harem and decides to turn the rest against him, so she becomes the main antagonist.
It could be that there is no traditional antagonist. The conflict might be internal, with Naruto's own emotions towards Kushina being the main source of drama.
It could be someone who is jealous of Naruto's hidden genius. Maybe a fellow ninja who senses that Naruto is hiding something and wants to expose him out of envy. This person might try to undermine Naruto at every turn.
A new character could be introduced as the main antagonist. Maybe a powerful ninja from another village who has infiltrated Konoha's politics. This character could be the one behind the idea of forcing Naruto back, with the intention of using Naruto as a pawn in a larger scheme against Konoha.
It could be a jealous Fairy Tail member. Maybe someone who is envious of Naruto's unique powers and the attention he gets from some of the guild members. This person could start spreading lies about Naruto to turn the others against him.
Maybe it's a powerful enemy from outside the village who has infiltrated the bingo book system. They see Naruto as a major threat to their plans and so secretly added him to the book, so they can send their minions to take him out without raising too much suspicion.
Perhaps the main antagonist is a corrupt official within the Hidden Leaf Village itself. This person was the one who arranged for Naruto's imprisonment in the first place and now that Naruto is out, they will do everything to stop him from uncovering their misdeeds. They might even team up with external enemies to achieve their goals.