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.
It could be a new villain who has risen to power during Naruto's absence. This villain might have a vendetta against Konoha or the ninja world in general because of something that happened while Naruto was away.
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.
A new dark entity could be the main antagonist. This entity might have been awakened by Naruto's return from the dead. It could be something that was sealed away long ago and Naruto's return breaks the seal. The entity would then target Naruto and his loved ones to prevent him from getting in its way of ruling the ninja world.
It could be a jealous demigod who thought that with Percy dead, they would be the most powerful or important one. Now that Percy is back, they see him as a threat to their status and plan to get rid of him again.
Perhaps a group of elite warriors in the new world who are jealous of Naruto's unique abilities. They form an alliance to take him down because they fear he will disrupt their status quo and take over their positions of power.
Maybe it's a new character who is jealous of Percy's status among the demigods. This new antagonist could be a powerful demigod from a different camp who has heard of Percy's feats and doesn't want him to steal the spotlight again. So, they try to use Percy's return from the dead as a way to turn the other demigods against him.
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.
Well, he might come back with new powers. For example, he could have learned some unique magic in the other world that gives him an edge in his own world's battles. Maybe he has new combat techniques or a different way of looking at heroics.
The Green Goblin could be a great main antagonist. Imagine in this other world, he has even more advanced gliders and pumpkin bombs. He could be ruling over a part of the city with his goblin minions, and Spider Man has to stop him from spreading his reign of terror further. His maniacal laugh and unpredictable nature would make him a formidable foe in this new world.
It could be an alternate version of Vlad Masters. In this other world, he might have achieved total domination over both the human and ghost realms. Danny would then have to face this all - powerful Vlad and find his weaknesses in this new context.