There could also be a new pirate crew led by a captain who has a grudge against both Natsu and the Straw Hat crew. This captain might have a Devil Fruit power that gives him an edge in combat against Natsu's fire and the Straw Hats' unique abilities, and his goal could be to take over the Grand Line and eliminate any potential threats, which includes Natsu and the Straw Hats.
It could be a powerful pirate crew that doesn't like the idea of an outsider like Naruto coming into their territory. They might see him as a potential rival for treasures or influence, so they try to drive him out or even eliminate him, thus becoming the main antagonists.
Perhaps an ancient being that was sealed away in both worlds long ago and is now awakened. This being could be extremely powerful, seeing the combined Naruto and One Piece universes as a threat or a source of power to be harnessed for its own dark purposes. It would be a formidable foe for Naruto and the One Piece characters alike.
Maybe an ancient dragon that has been awakened from its slumber and views Natsu as an intruder in the dragon world. Since Natsu is a new - made dragon, this old dragon might try to drive him out or even harm him.
It could be another dark mage who sees the potential in baby Natsu and wants to use him for evil purposes. This mage might view Zeref as an obstacle in getting to Natsu.
Maybe there's a dark wizard who has a vendetta against Natsu's family. When he finds out that Natsu is secretly a girl, he sees it as an opportunity to further his evil plans. He could try to kidnap her or use her as a bargaining chip against her family or friends. He might think that because she's a girl, she'll be easier to manipulate or capture compared to if she was thought to be male.
It could be a dark wizard who wants to use the baby's power for his own evil deeds. Maybe the baby has some special magic that the wizard thinks can help him take over the magical world.
Perhaps an existing 'One Piece' character could be turned into the main antagonist in the context of this fanfic. For instance, a marine officer who sees the OC as a threat to the world government's order. Since Viola has ties to Dressrosa, which has its own complex relationship with the world government, this marine could target them both. The officer might use underhanded tactics to try and stop the OC and Viola from achieving their goals.
It could be Zeref. Since he has a complex relationship with Natsu in the original story, he might manipulate things behind the scenes to make the Fairy Tail guild betray Natsu. Maybe he wants to isolate Natsu for his own evil plans.
It could be a time - traveling version of Zeref. He might be trying to stop Natsu from changing things in the past that could potentially lead to his own downfall in the future.
Perhaps an old enemy of Fairy Tail who sees Natsu as a new threat. They might target Natsu specifically to prevent him from strengthening the guild. This antagonist could have a long - standing grudge against Fairy Tail and see Natsu as the new hope for the guild, so they try to eliminate him before he can fully join.