It could be the remnants of old enemy clans who see Naruto as the last obstacle to their full control. For example, some rogue members of the Orochimaru - inspired groups might want to capture Naruto to extract his unique abilities since he's the last of his kind.
Well, it could be about Naruto having to face the loneliness of being the last. Maybe he has to carry on the traditions and values of his village all by himself. He might struggle with the weight of everyone's expectations and also deal with the memories of those he's lost.
It could be some rogue ninjas who are against Naruto's new peaceful policies as Hokage. They might see Hinata as a weakness to be exploited to get to Naruto.
It could be a rogue ninja who has developed a new and extremely deadly jutsu. This ninja has a vendetta against Konoha and was able to take out most of the ninja there, leaving Naruto as the lone survivor.
The main antagonists could be the remaining Titans who see Percy as the last obstacle in their plan to take over the world. Since Spartans were known for their great fighting skills, the Titans would want to eliminate Percy to ensure their victory.
It could be Orochimaru. He might be interested in the baby's unique genetic makeup, thinking he can use it to create more powerful experiments. He has always been obsessed with power and the baby's combination of Naruto and Temari's abilities would be very appealing to him.
The village elders could be the antagonists. They might have a hidden agenda and want Naruto out of the picture, so they imprison him unjustly.
Madara Uchiha could also be a possible antagonist in this scenario. Even if he is dead in the original story, in a fanfiction, his lingering influence or a resurrected form could manipulate Naruto. Madara was always against Konoha's ideals to some extent and might use Naruto as a tool to destroy what he hated.
One possible antagonist could be some of the traditionalist shinobi in the village who oppose Naruto's new family situation. They might see Kunou as a threat due to her heritage.
The Sound Ninjas could be great antagonists. They could use their own unique parkour - like skills to try and stop Naruto. They might be chasing him through the forest, and Naruto has to use his parkour skills to outmaneuver them.
The antagonists could be a secret organization within the Hidden Leaf Village itself. They are afraid that if Kurama is freed, it will bring destruction to the village. They think Naruto is being reckless and they will do anything to stop him, including framing him for crimes he didn't commit and turning his friends against him, all in an effort to keep Kurama sealed.