Maybe a new villain that is created specifically for this fanfiction. This villain could be a former student who was wronged by the hero society and now wants revenge. They would target both the real Class 1A and the 'Villain Class 1A' as symbols of the hero system they despise.
It could be All For One. He might see the 'Villain Class 1A' as a useful tool to further his own evil plans. He could manipulate them into doing his bidding, which would put them in direct conflict with the heroes, including Class 1A.
Perhaps an all - powerful villain from another dimension invades. This villain has the ability to control the minds of those with quirks and uses them to fight against the remaining heroes. He wants to take over the 'My Hero Academia' world and remake it in his own image. His powers are so strong that it takes all of the heroes' combined efforts just to try and figure out a way to stop him.
A group of villains who specialize in causing chaos during disasters could also be the main antagonists. They would constantly try to undermine Backdraft's efforts to keep the city safe during fires and other emergencies.
It could be the scientists or villains who turned Deku into a Noumu. They might want to use him for their evil plans, like taking over the hero society.
A possible main antagonist could be a scientist - turned - villain. This character could have created the situation where Deku needs oxygen in the first place. He might be obsessed with creating the 'perfect' hero and when Deku doesn't fit his mold, he decides to try and destroy him. The villain could use his scientific knowledge to create various obstacles for Deku related to his oxygen - dependent state.
It could be a rogue scientist. They might be jealous of the natural quirks that people are born with and decide to steal them to create artificial super - beings. They would be highly intelligent and use their scientific knowledge to develop devices or techniques to steal quirks.
It could be a powerful villain who sees Naruto as a threat to his plans in the My Hero Academia world. Maybe a villain who wants to use Naruto's unique abilities for his own evil purposes and when Naruto refuses, becomes his enemy.
Dabi could also be a main villain in such a fanfiction. His mysterious past and his powerful fire - based quirk would make for an exciting addition to UA. He could go to UA to spy on the heroes - in - training, but end up getting involved in their lives more than he expected. His cynical view of the hero society would clash with the positive environment at UA, and he might even start to question his own motives while there.
Perhaps an unknown entity that has possessed the doll. This entity could come from another dimension where evil rules. It uses the doll as a form to enter the My Hero Academia world and plans to take over. It starts by causing strange and unexplainable events, and as the heroes try to figure out what's going on, it gets stronger and more menacing.
Perhaps a powerful villain from the My Hero Academia world who is jealous of Naruto's power and wants to steal it for himself. He sees Naruto as a threat to his own plans of world domination and teams up with some of Naruto's old enemies from the Naruto universe to try and take him down. Midnight and Naruto then have to fight against this combined force.
A powerful dark sorcerer could be the main antagonist. He could be jealous of the heroes' quirks and see them as a threat to his magical dominance. He might start by cursing the heroes or stealing their quirks to add to his own dark magic.