Perhaps an ancient evil spirit that was once sealed away by the nine - tails long ago. Now it senses the nine - tails' presence in Naruto and wants to take revenge on it by destroying Naruto. This antagonist could have powers that are a match for Naruto and the nine - tails combined.
Another possibility is that the main antagonist is a group of power - hungry individuals who want to take Naruto's control of the Nine - Tails for themselves. They could be from within Konoha or from other villages. They might try to manipulate Naruto, or if that fails, they'll try to steal the Nine - Tails' power by force. They would likely be very skilled and have some devious plans up their sleeves.
Madara Uchiha could also be the main antagonist. Even if he was defeated before, in this fanfiction, he could come back with a new plan related to the Ten - Tails. He might want to use Naruto as a vessel to fully revive himself and then take over the Ten - Tails' power.
The Akatsuki could still be the main antagonists. They might be interested in Naruto's tails for their own dark purposes, like using their power to create a super - weapon or gain control over the ninja world. Another option could be a secret group of rogue ninjas who have a vendetta against the Uzumaki clan and see Naruto's tails as a symbol of their power that they want to destroy.
Dr. Eggman could still be the main antagonist. Even if Tails turns evil, Eggman might see him as a threat to his own evil plans. He could try to stop Tails while also taking advantage of the chaos Tails is causing among Sonic and his friends.
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.