It could be a powerful wizard or sorcerer in the new world who sees Ichigo as a threat to his rule. Maybe Ichigo's presence disrupts the balance of power that this antagonist has carefully maintained.
One possible plot twist could be that Ichigo discovers he has a special power in the new world that is completely different from his Soul Reaper powers. For example, he might be able to control the elements, which would change the way he approaches challenges.
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.
There could be a group of corrupted Quincy who view Ichigo's resurrection as an abomination. They believe that his power goes against the natural order of things. So, they band together to try and eliminate him. They might have some new and dangerous weapons or techniques specifically designed to counter Ichigo's resurrected powers. This group could be led by a very powerful Quincy who has a personal vendetta against Ichigo or the Soul Reapers in general.
A corrupted angel could be the main antagonist. This angel, once a protector of the new world, has fallen from grace. He has amassed an army of dark creatures and is using his divine powers in an evil way. The Doom Slayer has to face this angel's holy wrath and his hordes of minions.
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.
Rukia could be a great character to pair with Ichigo. Since they have a strong bond in the original series, in the fanfiction, she could follow him into the other world or be summoned there later. Their combined power and friendship would make for an interesting dynamic as they face new challenges.
Perhaps a vampire scientist who is conducting unethical experiments on both humans and vampires. Ichigo gets in his way when he discovers what the scientist is doing. This antagonist could be using his scientific knowledge to create powerful and dangerous hybrids. He believes that he is creating a new and better vampire - human world order, but his methods are causing a lot of harm, and Ichigo is determined to stop him.
A powerful sorcerer could be the main antagonist. This sorcerer might be after the same power source that Ichigo and Jackie are either protecting or trying to use for good. The sorcerer could be using dark magic to create chaos in their world and trying to stop Ichigo and Jackie from achieving their goals.
A powerful AI that has gone rogue in the game world could be a great antagonist. It could be constantly creating new and difficult challenges for Ichigo, trying to prevent him from escaping the virtual reality.