Perhaps an ancient evil that has been awakened. This entity is so powerful that Naruto has to rely on his Gear Second form more than ever. The antagonist's goal could be to destroy the ninja world and Naruto is the only one who can stop it in his enhanced state.
It could be a rogue ninja from a hidden village who has developed a power that can counter Naruto's Gear Second. This antagonist might be seeking revenge on Konoha for some past event.
A group of powerful missing - ninjas could band together to form the main antagonists. They target Naruto specifically because they fear his potential in the Gear Second form. They try to find ways to weaken him or steal his power, which sets up a series of intense battles in the fanfic.
Perhaps an old enemy of the Hidden Leaf who has resurfaced and is specifically interested in stealing the secret behind Gear Second. They could be a powerful and cunning foe, using various tactics to get close to Naruto and figure out how he activates and controls this power.
It could be Orochimaru. He might be interested in the Boosted Gear's power and try to steal it from Naruto. He has always been after powerful artifacts and new sources of power, so the Boosted Gear would be a great target for him.
It could be a rogue ninja from another village who has a vendetta against Naruto for his past actions in his first life. This ninja might see Naruto's second chance as an opportunity to finally get revenge.
It could be Orochimaru from the Naruto universe who somehow manages to infiltrate the Metal Gear world. With his knowledge of dark jutsus and his devious nature, he would make a great antagonist. He could start experimenting on the soldiers in the Metal Gear world, creating some sort of mutant - ninja - soldier hybrids.
The Organization in the Claymore world could be the main antagonist. They already have a lot of secrets and do some morally ambiguous things. If Naruto shows up and starts changing the status quo, like teaching Claymore warriors to be more independent, the Organization might see him as a threat and try to eliminate him.
It could be a rogue ninja who was once a student of Orochimaru and has now developed his own dangerous jutsu. He wants to take over the ninja world and believes the old ways are holding everyone back.
Orochimaru could be a great antagonist. He might want to use Shenron's power for his own dark experiments. He could try to steal the dragon balls and manipulate the wishes to gain immortality or create an army of powerful, immortal ninja.
It could be someone who opposes Naruto's newfound admiration for Ganondorf. Maybe a traditionalist ninja who thinks Naruto is straying from the true ninja path by getting influenced by Ganondorf.
Lex Luthor could be a great antagonist. He's always looking for power and knowledge. If he discovers Naruto's abilities, he might try to use them for his own gain or see Naruto as a threat to his plans in Smallville.
It could be Orochimaru. He's always been interested in unique powers and abilities. The idea of X - 23's mutant abilities and Naruto's jinchuriki powers would be very appealing to him. He might try to capture them both to use in his experiments to gain ultimate power.