A powerful sorcerer who wants to steal Izuku's Unlimited Blade Works power for his own evil purposes. He could be from a hidden world of magic and have minions that Izuku has to fight through.
An ancient being awakened from a long slumber. This being sees Izuku's power as a threat to its plans of ruling the world. It has the ability to manipulate reality and uses this to try and stop Izuku from fully mastering and using the Unlimited Blade Works power.
Maybe there's a villain group that targets Izuku specifically because of his money. They want to steal his wealth to fund their evil schemes. They might try to kidnap him or hack into his financial accounts. Izuku then has to use his wits as well as his money to outsmart them.
Lex Luthor could be a great main antagonist. He might see Izuku as a threat to his plans, especially if Izuku's unique abilities and sense of justice start to disrupt Luthor's schemes in the combined universe. Luthor could try to manipulate events to turn the Justice League against Izuku or find a way to steal Izuku's power for himself.
It could be Aizawa himself if he's being controlled by something or has some sort of ulterior motive that is not in Izuku's best interest. But if not Aizawa, then there could be a hidden villain who is manipulating Aizawa to kidnap Izuku.
One idea could be Izuku discovers he has the ability to use Unlimited Blade Works in a moment of extreme danger. He starts training with it secretly, trying to master the different blades and their unique powers.
Another option is that there is a group in his own world that doesn't like the idea of someone coming back from another world. They might see Izuku as an anomaly and try to capture or study him. This group could be a secret organization that has its own motives, and in their attempts to deal with Izuku, they end up being the main antagonists.
Perhaps a jealous classmate who has always been in Izuku's shadow. Now that Izuku is a girl, this classmate sees an opportunity to undermine her. They spread rumors about how Izuku's transformation is some sort of cheat or that she's not the same reliable person she was as a boy. This classmate's actions and attempts to sabotage Izuku would make them the main antagonist.
It could be a character who somehow discovers Izuku's secret and tries to use it against her. Maybe a rival at school who is jealous of Izuku's progress and sees this as a way to get her expelled or discredited in the hero community.
It could be a rogue ninja who was once part of the same clan that the hidden blade belongs to. He wants the blade back to gain ultimate power and is willing to do anything to get it from Naruto.
There could be an ancient evil entity that has been awakened by Godzilla's presence. This entity wants to destroy everything in its path and sees Godzilla and Izuku as obstacles. It has the power to corrupt other creatures and turn them against our heroes, making it a very formidable antagonist.
Danzo could be an interesting antagonist. He's a very secretive and power - hungry character. He might see a blade master as a loose end or a potential weapon that he wants to either eliminate or use for his own political gain in the Hidden Leaf Village. His underhanded methods would create a lot of conflict with a blade master who likely has a strong sense of honor.