Maybe the main antagonist is a secret organization within the hero society that doesn't want young heroes to grow up and change the status quo. Now that Deku is an adult, they try to eliminate him to prevent any potential changes he could bring to the hero world.
It could be an older version of a villain Deku has faced before. This villain has grown stronger over time and now that Deku is an adult, they see it as a chance for a rematch. They might also be jealous of Deku's rapid growth and new adult form.
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 villain who is obsessed with creating chaos through strange transformations. This villain might have targeted Deku specifically because of his status as a rising hero. They want to see how Deku will cope with being turned into a girl and use it to undermine his confidence and hero image.
Perhaps in the fanfiction, Deku turns into an adult due to a quirk malfunction. As an adult, he could struggle with his changed appearance and how his friends and family react. He might also find that his relationships with other characters, like Ochaco, change in unexpected ways as he is now an adult in a different stage of life.
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.
Obviously, Deku himself would be a main character even though he's turned into a baby. His friends like Uraraka, Iida, and Bakugo would also be main characters as they would be involved in taking care of him and trying to solve the problem.
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 an ancient dark wizard who has been manipulating events from the shadows. This wizard might see Elsword as a powerful tool and has been slowly influencing him to turn dark. The wizard could be using dark magic to cloud Elsword's mind and make him more susceptible to negative emotions.
Bowser could be the main antagonist. He might see Luigi's transformation as an opportunity to mess with Mario and the Mushroom Kingdom. He could try to use Luigi's new form to his advantage, perhaps by trying to make Luigi a spy or by using his new identity to cause chaos among the kingdom's residents.
Perhaps an evil mage who actually intended for the transformation to go wrong on purpose. They might want to use Sans' new female form to cause chaos in the Underground. They could be trying to manipulate Sans into doing bad things or using her to get to other important characters.
It could be a jealous rival. Maybe someone who has always been envious of Robin's abilities or popularity. Now that Robin is in a more vulnerable state as a girl, this rival sees an opportunity to undermine him.
It could be a witch who cast the spell that turned Dean into a girl. This witch might have some ulterior motives, like using Dean's new form to disrupt the balance in the hunting world. Maybe she wants to create chaos among hunters by making them question Dean's abilities now that he's a girl.