There could also be a new character created specifically for the fanfic. This character could be jealous of Naruto's second chance and the fame he had in his first life. So, this new antagonist tries to undermine Naruto at every turn and stop him from achieving great things in his second life.
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 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.
The main antagonist could be a corrupted version of Naruto himself from an alternate timeline. This 'evil Naruto' has different ideals and is bent on ruling the ninja world with an iron fist. In Naruto's second life, he has to not only face this powerful version of himself but also figure out how to stop his own dark tendencies from emerging.
It could be Orochimaru. In this fanfic, he could be a player of the same 'life - game' as Naruto, but with a much more sinister goal. He might be trying to manipulate the game rules to his advantage, like finding a way to make all the ninja in Konoha his puppets. Naruto would then have to figure out how to stop Orochimaru's evil plans within the game - like mechanics of his world.
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.
A new character could be created as the antagonist. For example, an Uchiha who has been corrupted by the power of the Sharingan and wants to use Naruto's special Uchiha - related abilities for his own evil purposes. This character could be jealous of Naruto's unique position within the Uchiha - related story and try to take it from him.