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.
An ancient being that has awakened from a long slumber. This being has the power to steal quirks and sees the modern quirk - users as a source of power. It has a different set of values and morals compared to the heroes and villains of the My Hero Academia world, making it a very unpredictable and dangerous antagonist.
Perhaps a disgruntled hero who has turned to the dark side. They feel that they were never given the proper recognition in the hero world despite their powerful quirk. So, they start stealing other heroes' quirks to prove their superiority and make a name for themselves in a more villainous way.
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.
One idea could be a villain who can steal quirks and is secretly a former hero trainee who was wronged. They start stealing quirks to create a super - powerful army to take revenge on the hero society that failed them.
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 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.
One cool quirk idea could be 'Shadow Mimicry'. The user can blend into any shadow and move freely within the shadow realm, also being able to mimic the actions of those whose shadows they are in. It gives a lot of stealth and surprise attack possibilities in a fanfiction.
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.