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.
In a crossover with another shonen anime universe, like the Bleach universe, it could be a powerful Hollow. This Hollow is attracted to Ace's strong spiritual energy (which could be related to his devil fruit power in some way). It wants to consume Ace to become even more powerful, and Ace has to use his combat skills and fire power, along with any help he can get from the Soul Reapers he meets in this new world, to defeat it.
Maybe an evil organization from a modern - day crossover setting. They might want to experiment on Ace to figure out the secrets of his devil fruit power and create super - soldiers. They would stop at nothing to get their hands on him, sending out their best agents and high - tech weaponry.
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.
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.
A powerful magical creature that has a grudge against both Harry Potter and Ace. It might see Ace as an intruder in its territory in the Harry Potter universe and Harry as someone who is interfering. So it tries to stop Harry from saving Ace and becomes the main antagonist.
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.
It could be a powerful pirate who has a grudge against Ace and Sabo's crew. This pirate might have some past history with them, like they were defeated by Ace and Sabo's crew in the past and now wants revenge.
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.
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.
If it's a crossover with Alice in Wonderland, the Queen of Hearts could be the main antagonist. The Queen might see Tinkerbell as an intruder and try to behead her. Tinkerbell would have to use her wits and magic to survive in the crazy world ruled by the Queen of Hearts.
The main characters are Ace, of course. Also, Luffy as his brother, and Whitebeard who was like a father figure to Ace. Blackbeard is also an important character as he was the one who led to Ace's downfall.