Well I wouldn't know if this idea is out there or not but I was thinking a storyline based on the upbringing of various trainers from start to finish. Basically you start off at the pokemon academy and go through various trials in order to graduate and become a trainer. For npc interactions I was thinking of a more buddy system so that players could have the opportunity to have a partner that isn't temporary for a particular setting. Players would have the chance to bond with npc characters during their playthrough and would possibly have to do buddy missions and so on to build up the affection meter. In this instance the gyms would be tag style unless they are forced to battle separately. The league could also be tag style until you reach the champion. Meaning that the npc also has to battle the champion or gym leaders before or after you. There will also be organizations and other criminal escapades going around in the meantime and maybe a few deaths may occur here and there. Not sure if it's an actual plot but it's simply the life of a trainer and their road to greatness or a simple life. The academy also has quizzes and tests but in the event you don't pass, the player has the option to either battle the examiners along with a fellow student in a tag match or drop out and join an organization or become a criminal.
The villain route will involve terroist attacks, stealing of pokemon, killing off unnecessary or potential obstacles in your or your affiliation's way along with other naughty deeds. Though there is a chance for the player to seek redemption and change their ways if they so choose to or even get the npcs you've formed a bond with to join you in your villainy. I would like all pokemon to be available if possible and there will be events for a selected bunch (some of which may require a sacrifice or so). Some buddy quest may require you to battle your rivals/friends or help them with their problems (simple stuff perhaps. boss battles may be included). I would like to have a travel option to the various regions so players could partake in events such as pokemon leagues, battle frontiers, pokemon contests, pokemon musical or theatre if that tickles your fancy, pokemon tournaments along other things (although the player must beat the league of a region in order to advance to the next one). A national pokemon league wouldn't sound too bad as you get to fight all types of powerful trainers (not sure if players would like characters from the main series as well as Red and Blue and so forth). Since some gym battles are tag based, either a custom trainer or an npc gym aide would be along with them. The national league champion would be a custom trainer who'll be helping the player in certain instances and predicaments without revealing that he is a champion. Artificial limbs would also be a thing for both players and npcs since accidents and so do occur after all. More things could be implemented but that's all I got for now at least. Though I'm pretty sure a game of this caliber would take a monstrous amount of time to produce.