The main antagonist could be a group of purist wizards who see Harry's disability as a sign of weakness. They might try to undermine his status in the wizarding world and prevent him from getting the help he needs. They could spread rumors about Harry, saying that he's no longer fit to be a hero, and try to isolate him from his friends and allies.
Perhaps the main antagonist is a curse that has a mind of its own. This curse could be the one that took Harry's leg and is now trying to prevent him from finding a cure. It could be an ancient and powerful curse that was accidentally unleashed in the wizarding world. The curse might be able to possess other people or objects to get in Harry's way as he tries to regain his mobility.
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 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.
It could be a new dark wizard who has a vendetta against Harry. This wizard might have created a spell specifically designed to target Harry's emotions, as he knows that Harry's strength often comes from his love and friendship. By taking away his emotions, he hopes to weaken Harry and make him easier to defeat.
Voldemort could be the main antagonist. He might have seen the potential in Harry's twin and decided to get rid of the twin to weaken Harry or use the twin for his own dark purposes.
Well, one possibility is that it could be about Harry's struggle to adapt to his new disability. Maybe he has to learn new magic or spells to help him move around. For example, he might discover a spell that creates a temporary prosthetic leg. Another idea could be that his friends rally around him, with Hermione researching ways to heal his leg completely and Ron being his emotional support. It could also show how he overcomes the challenges in his daily life at Hogwarts, like climbing the stairs or participating in Quidditch in a different way.
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 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.
The antagonist could be a cursed object. This object, which has some dark magic in it, might be found by Harry. And when he interacts with it, it starts to control his actions, leading to him breaking Ron's leg. So, in this case, the cursed object is the source of the trouble and can be considered as the antagonist in the fanfiction.
It could be an old enemy who takes advantage of Percy's weakened state. For example, Kronos might see this as an opportunity to finally defeat Percy and take over Olympus. Since Percy has lost an arm, Kronos might think he's more vulnerable and launch a new attack.
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.