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.
A new character could be the main antagonist. Imagine a rogue ninja who has hacked into the game system that controls Naruto's life. This ninja can change the rules, spawn powerful enemies, and generally make Naruto's life a living hell. Naruto has to find a way to outsmart this hacker - ninja and restore the normal game - life balance while also protecting his friends and the village.
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 an older and more powerful version of Orochimaru. In the new game plus scenario, he might have found a way to cheat death completely and has amassed an even greater army of experimental ninjas. He could be the main antagonist as he tries to take over the ninja world with his new - found powers and knowledge.
It could be Orochimaru. He is always looking for ways to gain power and in a game - like scenario, he could be the main villain trying to stop Naruto from achieving his goals. He might set up various game - like traps and challenges for Naruto.
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.