Maybe an old enemy of the village who has studied Naruto and Sasuke's relationship closely. He realizes that their bond is a key factor in the village's strength. So, he devises a plan to make Naruto forget Sasuke. He could be an ancient shinobi who was sealed away long ago and has now been released. His main goal is to weaken the village by severing this important connection between Naruto and Sasuke.
It could be a rogue ninja who has a vendetta against Sasuke. This ninja knows that Naruto's bond with Sasuke is strong, so he uses a special jutsu to make Naruto forget Sasuke, hoping to break Sasuke's spirit. By removing Naruto from Sasuke's life in this way, the rogue ninja believes he can defeat Sasuke more easily.
It could be an old enemy who has resurfaced, like Orochimaru again. Since Naruto and Sasuke are together now, Orochimaru might see them as a threat to his own plans for power and immortality.
One possible plot could be that Naruto suffers a head injury during a battle. As a result, he forgets about Sasuke completely. His friends initially don't notice, but as time passes, they realize Naruto's behavior towards Sasuke - related things is strange. For example, he doesn't get angry when Sasuke is mentioned like he used to. Then they try to help Naruto regain his memories of Sasuke through various means, like showing him old photos or taking him to places they used to go together.
Perhaps an ancient and malevolent spirit. This spirit might have been awakened by the Winchesters' activities and decides to target Dean. By making him forget his humanity, the spirit hopes to create chaos and destruction. The spirit could be using Dean as a pawn in its grand scheme to cause mayhem in the world of the living.
It could be someone who was also reincarnated from the Naruto universe but with a twisted sense of purpose. Maybe Orochimaru was reincarnated and is now using his knowledge of the past and new - found powers in this new world to cause chaos and try to stop Naruto and Sasuke from reuniting and fulfilling their new destinies.
It could be some of the village elders. They were the ones who decided to banish Naruto, so they could continue to oppose him even when he's in exile. They might see his growing power and influence as a threat to their traditional ways of running the village.
Obviously, Sakura and Sasuke are the main characters. Even though Sakura forgets Sasuke, their relationship (or the lack of it in this case) forms the core of the story.
It could be a new vampire who is jealous of Bella's relationship with the Cullens. This vampire might have some special power that allows them to manipulate memories, like Alice's memories of Bella. They see Bella as a threat to their own plans in the vampire world, so they try to create chaos by making Alice forget about her.
It could be Orochimaru. He's always had his eyes on Sasuke and Naruto has also been in his crosshairs. He could return with some new and more powerful jutsu, forcing Naruto and Sasuke to put aside their differences and fight him together. Maybe he has a plan to take over the entire ninja world this time.
Perhaps Danzo could be the main antagonist. He was always a bit of a shadowy figure in the original Naruto series. In this fanfic, he might see Naruto and Sasuke as a threat to his own control over Konoha. So, he uses his influence to have them banished. He could be secretly working with external forces to further his own agenda while keeping Naruto and Sasuke away from Konoha.
It could be someone from the Naruto universe who doesn't like Naruto's newfound fascination with Aku. For example, Danzo might see Naruto's interest in Aku as a threat to the stability of the village and try to stop Naruto from further exploring Aku - related things. So, Danzo could be the main antagonist in this case.