Perhaps the main antagonist is a spirit or a curse that has been awakened. This curse could be slowly influencing the villagers to turn against Naruto. It could be something that was sealed away long ago and now has broken free due to some mistake or interference. The antagonist could also be a mastermind from another hidden village who is using spies and psychological warfare to undermine Naruto's rule as the Sixth Hokage.
Sasuke could be a great choice. He has powerful abilities and a complex past. His experience as an avenger and then his redemption arc gives him a lot of depth. He has also learned from Naruto and has a different perspective on leadership. He could bring a more strict and strategic approach to being Hokage compared to Naruto.
It could be a rogue ninja from another village who has a vendetta against Konoha. Maybe he blames the Godaime Hokage for something that happened in the past, like the death of his family during a Konoha - related mission. So, he decides to target the village and the Godaime Hokage in particular.
Perhaps an old organization that was thought to be defeated resurfaces. They were biding their time while Naruto was hokage, and now that he's retired, they believe they can carry out their evil plans. They could be a group with a long - standing vendetta against Konoha and Naruto specifically. They might have new members or new powers that Naruto and his friends have to figure out how to counter.
Obviously, Naruto would be one of the main characters as it's about him becoming the sixth Hokage.
Naruto himself would be an obvious choice. He has the strength, the popularity among the villagers, and the experience from all his adventures. He would bring a new energy and a more inclusive approach to leading the village.
It could be a rogue ninja who was once a part of the Akatsuki but managed to escape before their downfall. He's been biding his time, growing stronger, and now he wants to take revenge on Naruto and the Hidden Leaf for what happened to the Akatsuki.
A group of rogue ninjas from other clans who oppose the idea of the Hidden Leaf Village. They see the Shodai Hokage's leadership as a threat to their own power and freedom. They might team up and use underhanded tactics like assassinations, sabotage of the village's resources, and spreading false rumors to try and undermine the Shodai Hokage's authority. They could also form alliances with other enemies of the village, making them a formidable and complex antagonist group.
It could be someone who wants to expose Naruto's secret. Maybe a rogue ninja who wants to use this information to create chaos in the village by making the villagers doubt Naruto's intentions.
It could be a rogue ninja who was once a part of Konoha but was banished for unethical experiments. Now, with a thirst for revenge against Naruto and the village, he returns as a powerful and unpredictable foe.
Sakura would be the main character as it's about her becoming the sixth Hokage. Naruto and Sasuke might also be important characters as they are her friends and have a big influence on the Naruto world.