I'm sure this is intended for the future at some point, but being able to block weapons/medallions from the item pool would be nice. Maybe a custom mode to be released with difficulty levels would be an easy way to implement this.
Along with that, a nuzlocke-style game mode that only allows you to take any item one time in a run could be interesting - probably unlocked after beating the game once or unlocking a certain number of weapons, tools, and medallions.