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.
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.
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.
One idea could be that Whitebeard is transported to a different time in the One Piece world. Maybe he ends up in the future and has to deal with new pirates and powers that he's never seen before. Another could be a crossover with another anime world, like he somehow gets stuck in the Naruto world and has to find his way back while dealing with ninjas.
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.
In many Whitebeard War fanfictions, Marco the Phoenix stands out. His ability to heal and his loyalty to Whitebeard are remarkable. Also, Squard is often a memorable character. His betrayal and then possible redemption can be a very interesting arc within the fanfiction. He adds an element of internal conflict within the Whitebeard Pirates which makes the story more complex.
In a fanfiction scenario where Luffy meets Whitebeard, it could be a really epic encounter. Luffy, being the carefree and determined pirate he is, might immediately show his respect for Whitebeard as a great pirate. Whitebeard, on the other hand, would probably be intrigued by Luffy's unwavering spirit. They could end up sharing stories about their adventures at sea, and perhaps Whitebeard would offer some words of wisdom to Luffy. Maybe they would even team up briefly to take on a common enemy, like some other powerful pirate crew that threatened the peace of the Grand Line.