I'm pretty disappointed with Resident Evil 5 overall, but by far my biggest complaint is the inventory system. Nine slots per character is not nearly enough. Carrying two weapons, with ammo, is already using up almost half your space. Pick up some grenades and healing items, and you wind up running out of room constantly. Therefore you wind up leaving stuff in your magic, traveling inventory space, which you access by... Restarting the game from your last checkpoint? It destroys the flow of the game and feels incomplete, and a bit like cheating. I ended up with stockpiles of first aid sprays by the end of the game, because I figured I'd save them for later since I had no room, the end of the game came pretty fast and the inventory expansions I assumed were coming (because there's no way they'll expect me to play the entire game like this, right?!) never showed up. When a first aid spray is not a hot commodity you have balance problems.
So this one issue basically ruined the game for me. I wound up with 20+ of every type of grenade because I would just dump them in inventory and Sheva sure as hell wasn't using them. I almost never used the grenade launcher or the magnum, and there was little need to, unlike RE4. I would find myself lugging around the sniper rifle, deciding that a slot for the gun and another slot for its ammo was too much and sticking it in inventory, only to need to reload a checkpoint to pull it out of inventory when I would need it.
Beyond that the story is super-generic (and super-predictible) and the game is SHORT. It has its moments but compared to its predeccesor, this game just doesn't hold up.