Perhaps an old enemy of Deku who has a grudge against him. This antagonist might have found a way to use a powerful artifact or quirk to make Deku lose his memory. Their goal could be to break Deku's spirit and make him give up on being a hero. They might also try to turn Deku's friends against him while he's in his vulnerable state.
There could be a group of villains working together. One of them has the ability to erase memories, and the others see the opportunity to use Deku's memory loss to their advantage. They might try to make Deku believe that he was one of them all along, and persuade him to use his powers for evil. This would create a really interesting conflict as Deku has to fight against false memories and the influence of these villains.
It could be a new villain who has the power to manipulate memories. This villain might target Deku specifically because he sees Deku as a threat to his plans. He wants to erase Deku's memory so that he can't interfere with his evil schemes in the hero world.
It could be Orochimaru. He's always been interested in Naruto's power. Maybe he devises a plan to make Naruto lose his memory so he can manipulate him more easily, perhaps to use him as a weapon against the Hidden Leaf.
It could be a marine admiral who has developed a new weapon that not only causes physical harm but also memory loss. This admiral might see Luffy as a big threat and decides to use this weapon on him to weaken the Straw Hat crew.
Well, one possible plot could be that Deku gets hit by a villain's quirk during a battle. This quirk erases his memory. His friends, like Uraraka and Iida, then try to help him remember who he is. They might show him his hero notebook, hoping it jogs his memory about his dream of becoming a great hero.
Another possibility is that a new villain emerges as a result of the time - travel or whatever mechanism brings future Deku to the present. This villain could be from a future where Deku's actions (or inactions) have led to a more dangerous world, and he travels back in time to stop Deku from making those mistakes again. However, his methods are extreme and dangerous, making him the antagonist of the story.
A new villain could emerge who is specifically targeting adult heroes. Since Deku has now become an adult, he becomes a prime target. This villain might have a grudge against the hero society's adult leadership and see Deku as a symbol of that.
It could be a new and powerful rogue ninja who manages to overpower Naruto and cause him to lose his arm. Maybe this antagonist has some sort of vendetta against Naruto or the Hidden Leaf village.
It could be a new dark wizard who has a vendetta against Harry. This wizard might have specifically targeted Harry's leg as a way to cripple him both physically and mentally. Maybe this antagonist has some sort of connection to Voldemort's old followers, seeking to finish what Voldemort started.
It could be Zuko if the fanfiction takes a different turn. Maybe Zuko, still struggling with his own inner demons, sees Aang's loss of control as an opportunity to take advantage and gain power. So he tries to manipulate the situation to his benefit.
It could be an old enemy like Kronos. Kronos is extremely powerful and cruel. He might target Percy's eye as a way to weaken him both physically and mentally. By taking away Percy's eye, Kronos hopes to make Percy less effective in battle and to shatter his confidence, which is crucial for leading the demigods against him.
It could be Voldemort, even if he's already been defeated in the original story. His lingering influence might still haunt Harry. Maybe there are some dark magic remnants of Voldemort that keep causing problems and making Harry feel hopeless.