Well, the main antagonists could be a group of rogue ninja who are hired by a powerful nation to take down Naruto. Since he is unkillable, they would have to use more underhanded tactics like trying to isolate him from his friends and allies. Or perhaps there is a dark force that is awakened by Naruto's unkillable state, thinking that he is a threat to the balance of the ninja world. This dark force could then become the main antagonist, trying to destroy Naruto at all costs.
Well, in such a fanfiction, Naruto might be unkillable because of some special power-ups. Maybe he has some kind of indestructible chakra shield that constantly protects him from any harm. It could also be due to a unique bond with a powerful entity that grants him immortality. Another possibility is that his willpower is so strong that it literally defies death, allowing him to survive any fatal situation.
Maybe there are powerful dark sorcerers. These sorcerers could be trying to capture Naruto for their own evil purposes, like using his power to open a portal to a dark dimension or something, and Kurama has to protect him from them.
Another type of antagonist could be a strict professor who doesn't like Naruto's carefree attitude and Hinata's association with him. The professor might try to give them a hard time, like assigning them extra difficult projects or being overly critical in class, which becomes an obstacle in their college life and relationship.
Anko might not be a traditional antagonist, but if she is siding with Evil Naruto for some reason, she could be seen as an antagonist from the perspective of the other villagers. However, it's also possible that she is being manipulated herself, in which case the true antagonists would be those doing the manipulating.
It could be some rogue ninjas who are against Naruto's new peaceful policies as Hokage. They might see Hinata as a weakness to be exploited to get to Naruto.
Well, it could be a group of rogue shinobi who profit from war and chaos. They don't want Naruto to succeed in bringing peace because it would mean an end to their lucrative and power - hungry ways.
Perhaps there is a powerful and mysterious figure lurking in the shadows of the Blood Prison. This character has a vendetta against Naruto and uses the prison's environment and its inmates to try and bring Naruto down.
Often, it could be rogue ninjas. They might target Ino because of her family's importance in the village, and Naruto gets forced into protecting her. These rogues can be after some secret technique that Ino's family guards. Another antagonist could be a power - hungry shinobi from another village who wants to use Ino as a pawn to gain leverage over Konoha. Naruto then has to step in and stop them.
Maybe there's a rogue ninja who has developed a new and dangerous jutsu that can counter Naruto's powers. This ninja wants to prove himself as the strongest by defeating Naruto and taking over the bijuu's power. He might be jealous of Naruto's newfound status and the respect he gets from the other ninjas.
Often, it could be a group of rival students from another college who are jealous of Naruto and Sakura's skills or achievements. They might try to sabotage their projects or disrupt their college events.