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.
Another option for the main antagonist could be a corrupted version of one of Whitebeard's own crew members. This character could have been influenced by some dark power and now wants to take over Whitebeard's position. They would know all of Whitebeard's weaknesses and strategies, making them a very formidable foe for the crew.
It could be a powerful sorcerer from a magic - based crossover world. This sorcerer sees Ace's power as a threat to his own rule and plans to either capture Ace and use his power for his own evil deeds or simply destroy him.
Maybe it's a new pirate crew led by a character with a Devil Fruit power that can nullify the OC's Gamer abilities. This pirate captain is extremely ambitious and wants to rule the New World. He views the OC as an obstacle in his path because the OC has the potential to disrupt his plans, especially if they can use their Gamer skills to form alliances against him.
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.
It could be a dark wizard who wants to use Natsu's connection to the Dragonoid for his own evil purposes. This wizard might have set the trap to either steal Natsu's power or to use him as a sacrifice to gain more power related to the Dragonoid.
It could be an old and powerful vampire lord who sees Natsu as a threat to his rule. Since Natsu is a new and different kind of vampire, the lord might want to eliminate him.
It could be a long - lost relative of an old enemy. For example, if there was a powerful dark wizard that Natsu defeated in the past, this relative might come seeking revenge and be powerful enough to kill Natsu.
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.