Maybe a new character created specifically for this crossover. A being that is jealous of Naruto's power and wants to harness it for their own evil purposes. This new antagonist could be a hybrid of some sort, combining the dark aspects of both Naruto's world, like dark chakra, and the malevolent traits of the Twilight vampires.
Another possibility is that the werewolves could become the main antagonists. If Naruto's actions somehow disrupt the delicate balance between the vampires and werewolves in Twilight, the werewolves might see him as an enemy. Especially if Naruto's power is misinterpreted and they think he's siding with the vampires.
It could be one of the powerful vampires from Twilight. For instance, if they see Naruto's 'godlike' abilities as a threat to their way of life or power structure, they might oppose him. Aro, with his mind - reading ability and his ambition to control the vampire world, could be a likely candidate.
Maybe an ancient being that was sealed away long ago in the RWBY world but has now been awakened by Naruto's arrival. This being, with its own set of dark powers, sees Naruto as a threat to its plans of domination. It starts to create chaos, summoning Grimm in large numbers and using some form of corrupted chakra - like energy to attack. The RWBY characters and Naruto would have to put aside their differences and combine their skills to defeat this powerful foe.
Maybe an evil scientist from the Lab Rats' world who has heard of Naruto's godlike powers and wants to harness them for his own experiments. He could create powerful robotic minions to fight Naruto and the Lab Rats. This scientist could be jealous of the Lab Rats' abilities and see Naruto as a new source of power to take over both worlds.
It could be another god - like being who is jealous of the female character's powers or her influence in the Naruto universe. This antagonist could be from the same realm as the female character but has different motives. He or she might want to use the chaos in the Naruto world to gain more power for themselves, and the female character stands in their way.
Another possibility is a powerful spirit from the Avatar world that has been corrupted by the introduction of Naruto - like powers. This spirit could resent the intrusion of this new power source and seek to destroy anyone associated with it. It might have unique abilities that combine the spiritual magic of the Avatar world with the raw power of Naruto's chakra, making it a formidable foe.
There's also the possibility that a group of rogue ninjas, who have banded together after being ostracized for their interest in the godlike hollow powers, become the antagonists. They might believe that Naruto is misusing or hoarding these powers and decide to take them by force, leading to a series of intense battles between them and Naruto.
Perhaps a dark entity from another dimension. This entity senses Naruto's powerful bloodline and wants to possess him or use his body as a vessel to enter the Naruto's world and wreak havoc. It would have otherworldly powers that Naruto has never faced before, making it a truly formidable antagonist.
It could be a combination of Orochimaru and Lex Luthor. Orochimaru from the Naruto universe is always seeking power and Lex Luthor from the DC universe is a brilliant but evil mastermind. They could team up, with Orochimaru being interested in Superman - like Naruto's unique physiology and Lex Luthor wanting to use Naruto's power to take over both the Naruto world and the DC world. They would be a formidable duo, constantly devising plans to undermine Naruto and his friends.
The Volturi could be the main antagonists. In the Twilight universe, they are the powerful vampire coven that enforces the vampire laws. They might see femNaruto's presence as a disruption to their carefully maintained order. Her different powers and her way of thinking could be a threat to their authority.
The Dark King from Sailor Moon could team up with the Volturi. The Dark King's thirst for power combined with the Volturi's strict vampire laws could create a really menacing force. They could be trying to take over both the magical world of Sailor Moon and the vampire - filled Twilight world.
It could be a powerful ninja from an ancient clan who sees the character with the godlike multi - bloodline as a threat to their own clan's supremacy. This antagonist would be very skilled in traditional ninja arts and would use their knowledge of the old ways to try and defeat the protagonist.