It could be a powerful vampire lord who sees the hybrid as an abomination and wants to destroy them. This vampire lord might view the mixing of werewolf and vampire blood as a threat to the purity of the vampire race.
Maybe an ancient werewolf alpha who doesn't want any vampire influence in their territory. The hybrid, being a combination of both, is seen as a trespasser and a threat to the werewolf pack's way of life. The alpha could gather a group of werewolves and start a war against the hybrid and anyone who protects them, including Naruto and his friends.
It could be a powerful vampire hunter who believes Naruto, as a new vampire, is a threat to the balance between humans and vampires. This hunter might be from a long line of slayers and is determined to eliminate Naruto before he fully embraces his vampire side.
There could be a really interesting story where Naruto, with his ninja skills, adapts to being a vampire - werewolf hybrid in the Twilight world. Maybe he uses his shadow clone jutsu to confuse other vampires or werewolves. He could also bring in his own sense of honor and friendship from the Naruto universe into this new and dark world of Twilight.
It could be an old - fashioned vampire who doesn't like the idea of hybrids and sees Caroline as an abomination.
It could be a rogue ninja who wants to capture the female werewolf for her unique powers. He might see her as a tool to gain more power in the ninja world.
Perhaps a group of vampires who are trying to take over the entire Rosario Vampire world and are causing harm to both humans and other supernatural beings. Naruto views their actions as unacceptable and makes it his mission to banish them. They could be very strong and have some special abilities that make them a formidable foe for Naruto.
Well, Naruto is known for his big heart and loyalty. In this fanfiction, he might use those traits to bridge the gap between the vampires and werewolves. He could see that they don't have to be enemies all the time, just like he saw that there was more to people in his own world than just their differences. His hybrid nature could give him a unique perspective on their long - standing feud.
Maybe the Ministry of Magic could be the main antagonist. If Harry turns into a hybrid, the Ministry might see him as a dangerous abomination. They could try to capture him and keep him locked away, thinking that his new form is a threat to the wizarding world's order. They might not understand that Harry is still the same person inside and that his new form could actually be an asset in the fight against evil.
It could be the werewolf who bit Harry. Maybe the werewolf has some ulterior motives, like using Harry as a pawn in a bigger plan against the wizarding world. Or it could be some pure - blood wizard supremacists who see Harry's new werewolf status as a sign that he is now 'impure' and want to get rid of him.
It could be another vampire clan. They might see Cartman and Kyle's relationship as a threat to their own power or way of life. For example, if Cartman and Kyle are trying to promote co - existence between vampires and humans, the other clan might oppose it.
One possible plotline could be that Naruto is somehow turned into this werewolf - vampire hybrid. He then has to struggle with new powers and instincts. For example, he might have the werewolf's enhanced strength and sense of smell along with the vampire's ability to hypnotize or super speed. And he has to keep this a secret from his friends in Konoha while also fighting against new enemies who are either after his new powers or are also some sort of hybrid or supernatural beings.