Perhaps the main antagonist is an organization that wants to create an army of Noumu - like Deku. They see Deku as the perfect prototype and will stop at nothing to replicate his transformation. They send their own enhanced villains after Deku to capture him alive, and these villains, with their unique and dangerous abilities, pose a great threat to Deku and his friends throughout the fanfiction.
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.
The main antagonist could be a powerful villain who sees Deku, now as a Noumu - like being, as a threat to his own plans for domination. This villain could be someone new, not from the original series, who has a special ability to control or nullify Deku's Noumu powers. He might try to manipulate Deku into joining his side or simply try to destroy him to eliminate the threat. The hero society might also be an antagonist in a way, as they are scared of Deku's new form and try to hunt him down, which forces Deku to fight back against those he once considered allies.
In a 'My Hero Academia Noumu Deku' fanfiction, the plot could involve Deku being turned into a Noumu - like creature against his will. This transformation could lead to him being shunned by society at first. However, he could use his newfound strength, along with his unwavering hero spirit, to prove that he's still a hero at heart. He might team up with some unlikely allies, like villains who also oppose the unethical experiments that created him.
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.
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.
Toga could be an ally. Since she has her own complex relationship with the idea of heroes and villains, she might find Deku's transformation interesting. She could provide some of her unique skills, like shape - shifting, to help Deku in his villainous plans. Additionally, Twice might also join them because of his loyalty to Toga and his own sense of being an outcast in the hero world.
It could be a group of villains working together. For example, the League of Villains might decide to kidnap Deku. They might want to use him as a bargaining chip against the heroes. Or it could be a rogue hero who has turned to the dark side. This hero might think that Deku is getting too much attention and kidnaps him to take his place in the spotlight.
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.
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.