It could be some of her jealous peers. For example, those who are envious of Sakura's skills or her closeness to certain important characters in the Naruto universe. They might spread malicious gossip about her to make her an outcast.
In some cases, it could be a mysterious figure from outside the village who is trying to undermine the unity of the village. They target Sakura and make her seem like a danger to the village, causing the villagers to turn against her.
Perhaps the elders in the village who have traditional views. They might see Sakura's new ideas or unorthodox ways as a threat to the established order in the village. So they use their influence to ostracize her.
One possible antagonist could be a popular girl in school who is jealous of Sakura's popularity and tries to undermine her at every turn. For example, she might spread false rumors about Sakura or try to steal her friends. Another could be a strict teacher who doesn't believe in Sakura's abilities and is always giving her a hard time, like constantly doubting her work in class or not allowing her to participate in certain school activities.
Danzo could be a great antagonist. He might see Sakura's prodigious abilities as a threat to his power and control in the village. He could try to undermine her at every turn, whether it's by sending assassins after her or trying to discredit her in the eyes of the villagers.
There could be a powerful ayakashi leader as the main antagonist. This leader might be controlling the other ayakashi and specifically targeting Sakura Haruno for some reason. Maybe it's because of her latent power or her connection to a certain place or person. The other ayakashi would then be minions following this leader's orders in the fanfiction.
Another possible antagonist could be a jealous relative. For example, a cousin who believes they should be the heir instead of Sakura. This relative could spread false rumors about her, or try to sabotage her efforts to prove her royalty in more subtle ways, like stealing important documents or artifacts related to her claim to the throne.
In certain 'sakura haruno revenge fanfiction', Orochimaru might be the antagonist. Given his history of using people for his experiments and causing harm, Sakura could decide to take revenge on him, perhaps to stop his evil plans and avenge those who have been affected by his actions.
One possible storyline could be that Sakura is outcast because she has developed a new and unorthodox ninja technique that others are afraid of. So she has to struggle alone, trying to prove its value.
It could be rival assassins. They might see Sakura as a threat to their own business or reputation in the assassin world.
It could be an envious noble. This noble might be jealous of Sakura's position as a princess and her popularity among the people. So, they try to spread false rumors about her and plot to dethrone her.
Sakura might meet the founders of the village. For example, she could meet Hashirama Senju. He was a powerful and visionary leader. Meeting him could give Sakura insights into the true origins of the village and how to better protect it. She could also learn some of the ancient ninja techniques from him.
The Akatsuki could also serve as antagonists. Even if Itachi was once part of them, they might target Sakura to get to Itachi or to use her skills for their own evil purposes. Their goals of collecting tailed beasts and causing chaos in the ninja world would clash with Itachi and Sakura's efforts to protect the village and each other.