Perhaps a group of villains could be the main antagonists. They could be a cult of magic - users who worship an ancient and evil magical entity. Their plan could be to bring this entity into the world by performing a dark ritual. The heroes would have to fight against this cult, which has members with various powerful and dangerous magic spells at their disposal.
It could be All for One, but in a more magically - powered form. Instead of stealing Quirks, he steals magic spells and powers from other magic - users. His goal could be to become the most powerful magic - user in the world and rule over all the magical kingdoms.
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.
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.
The support class students could be the main characters. They are always in the background creating amazing gadgets for the hero students. Hatsume Mei, for instance, could be shown as she works on her inventions in her workshop, and how she interacts with the other support students and the hero students secretly. They could be the ones who actually have a big influence on the heroes' success but are not always in the spotlight.
A great plot idea would be a mystery - centered one. In this 'My Hero Academia Fantasy AU Light Novel', there could be a series of strange magical events occurring in the world. The characters have to use their unique magical abilities (like Todoroki's ice and fire magic) to solve the mystery. Maybe there's a dark magic user trying to disrupt the balance of the magical world, and the heroes must stop them before it's too late.
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 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.
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.