Maybe Orochimaru could be the antagonist. He hears about Naruto's encounter with Yagura and wants to use their connection for his own evil experiments. He might try to capture Yagura again (if he was once under Orochimaru's control) or manipulate Naruto into doing something that would harm Yagura and the relationship between the two villages.
The antagonist could be a powerful dark spirit that has been possessing Yagura and making him act in a negative way. Even after Naruto meets Yagura, this dark spirit tries to regain control and cause destruction. Naruto has to not only fight against the physical manifestations of the spirit but also figure out a way to exorcise it completely from Yagura.
The plot could involve Yagura being freed from the control of the evil forces that once manipulated him. Naruto, being the hero he is, senses something strange about Yagura. He then uses his shadow clones to investigate. When he discovers the truth, he uses his chakra to break the hold on Yagura. After that, they form an alliance to help the Hidden Mist Village recover from the damages caused by Yagura's previous actions under control.
Naruto might approach Yagura with honesty. He would probably start by telling Yagura that he knows he's in a bad situation with the Akatsuki. Naruto could share his own story of being ostracized in Konoha at first and how he overcame it. This would make Yagura see that Naruto can understand his pain and might be more receptive to Naruto's help.
It could be that Yagura had some secret plans that would endanger the balance among the ninja villages. Naruto, having a strong sense of protecting peace, discovers these plans and decides that eliminating Yagura is necessary. For example, if Yagura was planning to use a powerful and dangerous jutsu that could destroy multiple villages, Naruto would act to prevent it even if it means killing him.
In fanfiction, the 'Naruto x Yagura neglect' could imply a relationship where Naruto is somehow involved with Yagura, but there is neglect present. This might be explored in terms of their character interactions. For example, if Naruto fails to understand Yagura's past traumas which leads to a form of neglect in their relationship. It could also be a situation where the storyteller is trying to show the consequences of such neglect on both characters' development and how they deal with the emotional fallout.
It could be a powerful alchemist who has gone rogue and wants to use Naruto's chakra for some dark alchemy purpose.
It could be someone who wants to steal Samehada for its power. Maybe a rogue ninja who has heard of Samehada's ability to absorb chakra and plans to use it to take over the ninja world.
It could be an ancient evil that Rikudou Sennin once sealed away. With Naruto and Rikudou Sennin meeting, this evil might sense an opportunity to break free and becomes the antagonist.
Maybe a powerful rogue ninja who has discovered a way to steal the powers of divine entities. He sets his sights on Amaterasu and Naruto because he knows that if he can combine their powers, he will be unstoppable. He creates various traps and illusions to separate them and weaken them so that he can carry out his evil plan.
It could be a rogue ninja who is after Sakumo's hidden techniques. Since Naruto meets Sakumo, this rogue ninja sees Naruto as an obstacle and tries to eliminate him. This antagonist might have a grudge against the Hatake clan and wants to use Sakumo's secrets for his own evil purposes.
Maybe a rogue ninja who has somehow tapped into dark powers related to Kami's domain. This ninja wants to use these powers to take over the ninja world, and Naruto, with Kami's help, has to stop him. In this fanfiction, the rogue ninja could have some personal vendetta against Kami as well, which adds more depth to the story.