There could be a mysterious organization that has been hidden for a long time. They emerge when Sasuke and Sakura start their journey. This organization wants to use Sasuke's power and Sakura's medical knowledge for their own evil purposes. They set up traps and send assassins to target the duo throughout their journey.
In some fanfictions, there could be a group of rogue ninjas who form an alliance during the war. They have no loyalty to any particular side and are only interested in causing mayhem. Sasuke and Sakura would have to deal with their unpredictable attacks and devious plans.
In some fanfictions, there could be a co - worker who has a secret crush on Sasuke or Sakura. This co - worker then tries to drive a wedge between them by spreading rumors or causing misunderstandings in the office environment.
It could be an original character created just for the fanfiction. Maybe a powerful ninja from a forgotten clan who has a vendetta against Konoha and targets Naruto, Sasuke and Sakura specifically.
Perhaps the antagonist could be a teacher who has a dark secret. This teacher might be using the students for his or her own gain. Sasuke and Sakura notice some strange behavior from this teacher and start to suspect that they are up to no good. They then become the targets of this teacher's wrath as they get closer to uncovering the truth.
Perhaps there is an ancient evil entity that feeds on the hatred between werewolves and vampires. It doesn't want Sasuke and Sakura to succeed in bringing peace. So it uses its dark magic to create misunderstandings and conflicts between the two, trying to keep them at odds and prevent any chance of unity.
There might be some ancient forces or entities that are awakened by Naruto and Sasuke's new 'godlike' status. These could be demons or spirits that were sealed long ago and now see Naruto and Sasuke as threats to their plans of domination. They would be very powerful and require Naruto and Sasuke to use all of their enhanced abilities to defeat.
Well, it could be about their journey to find a lost ninja art. They might face various challenges and enemies along the way. Their relationship could also develop during this journey, from just being comrades to something deeper.
Another possibility is a rival pirate hunter. Someone who is jealous of Sakura's skills or success and tries to get in her way, perhaps by spreading false rumors about her or even directly interfering with her missions.
Another possibility is a rival clan. They might target Sakura specifically because she is seen as a rising star within her clan and they want to undermine her clan's strength. For instance, they could try to kidnap her or spread false rumors about her to create discord within her clan.
One possible main antagonist could be a shinobi from another village who fears Sakura's potential as Hokage. This shinobi might try to undermine her by causing chaos in her village or spreading false rumors about her abilities. Another could be someone within her own village who has a long - standing grudge against her or her family and doesn't want to see her in a position of power.