There might be a group in the future that is against any interference from the past. They view Sakura as an intruder and will do anything to send her back or keep her from changing the future in any way. They could be a secret organization that has been protecting the future's timeline and see Sakura as a potential disruptor.
It could be a time - traveling villain who doesn't want Sakura to succeed in her journey in the future. This villain might be from Sakura's own time but has different motives in the future setting.
Well, it could be about Sakura finding herself in a future world full of advanced technology. Maybe she has to adapt to new ways of life and use her skills from her own time to solve problems there.
In this fanfiction, the main antagonist could be a strict teacher. Sakura, being a boy with a free - spirited nature, often clashes with the teacher's rigid rules. The teacher always seems to be out to get Sakura, giving him unfair punishments and trying to suppress his creativity or individuality.
The Joker could be the main antagonist. Even though Batman is in jail, the Joker could find a way to continue his chaos - making. He might try to get into the prison to torment Batman or use the situation to his advantage by causing mayhem in Gotham City without Batman there to stop him.
Maybe it could be a new character who is a combination of ninja and wizardry evils. This character could be jealous of Naruto's unique abilities that bridge the gap between two different worlds and wants to stop Naruto from uniting the ninja and wizarding communities against him. They could have powers that are a mix of dark magic and some dark ninja jutsus.
A powerful sorcerer could be the main antagonist. He might be after Percy's powers or trying to use the school as a base to spread chaos. Maybe he wants to open a portal to the underworld right in the middle of the schoolyard.
Perhaps a new, powerful demigod - vampire hybrid that Percy has to face. This hybrid could be causing trouble in Forks, and Percy has to stop it before it destroys the delicate balance between the vampires, werewolves and humans there.
There might be a character who is secretly from the wizarding world but has turned to the dark side. This character could be after Harry in the Ouran setting, trying to use the chaos of the new environment to their advantage to get to Harry without being noticed by the Hogwarts professors.
It could be a new dark wizard that we haven't seen in the original series. This wizard might be jealous of Harry's fame and power and wants to eliminate him by making him disappear.
The main antagonist could be Naruto himself in a sense. Since he has gone insane, his actions are now unpredictable and harmful to the people around him. His former friends, like Sakura or Kakashi, might have to step up and try to stop him, seeing him as the new threat.
The Hidden Leaf Village itself could be the main antagonist. If they turn on Naruto for no good reason, they become the force he has to fight against as a rogue ninja.