You might consider a fanfiction where the main character has the ability to communicate with the Mold, and through this connection, tries to find a way to end the cycle of horror in the village once and for all. This would involve exploring the nature of the Mold, its intelligence (if any), and how it affects the inhabitants of the village both physically and mentally.
A cool fanfiction plot might be to introduce a new character who has a special ability to communicate with the infected. This character could either help Leon or create new challenges for him as he tries to rescue Ashley.
One idea could be exploring the backstory of the Baker family in more detail. Maybe how they got infected in the first place and what their lives were like before the events of the game.
One idea could be exploring the backstory of the secondary characters more in - depth. For example, what was the life of the police officers in Raccoon City before the outbreak? Another could be a different take on how the main characters like Leon and Claire met and teamed up. Maybe they initially had some misunderstandings before realizing they needed to work together to survive.
One idea could be exploring the backstory of Lady Dimitrescu's daughters in more detail. Maybe how they came to be and their lives before Ethan Winters arrived.
One idea could be that Naruto and his team are sent to the Resident Evil universe to find a cure for a virus that has started to infect the Hidden Leaf. They would have to face off against zombies and bio - weapons using their ninja skills. Another plot could involve a Resident Evil character getting transported to the Naruto world and having to adapt to chakra and ninja society. For example, Leon Kennedy could team up with Naruto to stop a bio - terrorist attack in Konoha.
A possible plot is that some of the characters from Naruto are experimented on by the Umbrella Corporation. Sasuke, for instance, could have his Sharingan enhanced in unexpected ways due to the unethical experiments. This would lead to a power struggle within him as he tries to control his new abilities while also dealing with the fact that he has been turned into a sort of bio - weapon. And then Naruto would have to find a way to save him without getting infected himself.
A plot idea could be that there are hidden survivors in the areas affected by the virus in Resident Evil 5. These survivors have developed their own ways to resist the virus and they form an alliance with Chris and Sheva. They could share knowledge about the virus that was previously unknown, like a natural antidote that exists in a certain rare plant in the area. Also, what if the main villain had a change of heart mid - way through the story? Maybe they realize the horror they've unleashed and try to help Chris and Sheva stop it, but their past actions still haunt them and make it difficult for the heroes to trust them.
One idea could be an OC who has a unique connection to the Tyrant. Maybe they were part of the experiment that created it and now they have a psychic link. They could use this link to try and control the Tyrant's actions, which would create a lot of tension as they battle their own inner demons while also trying to stop the Tyrant from causing more chaos.
One idea could be creating an original character who is a scientist that was once part of the same research team as Simmons but had a change of heart. This oc could be on a mission to expose the real motives behind the C - virus outbreak. Another idea is an oc who is a skilled martial artist that teams up with Leon and Helena to fight off the infected in a city. They could bring a unique fighting style to the story.
Well, a cool fanfiction concept could be that some of the Resident Evil villains get transported to the Naruto universe. For example, Albert Wesker shows up and tries to take over the ninja villages using his superhuman abilities and intelligence. Or perhaps the Resident Evil bio - weapons are let loose in the Naruto world and the shinobi have to figure out how to deal with these new threats that are completely different from their usual enemies like other ninja clans or rogue ninjas.