There are 2 NPCs in SMB,
both of which are kind of playable eventually. I don't think that'll make an interesting plot, honestly.
Super Mario RPG got around that by designing two new playable characters, Mallow and Geno. The first Mario & Luigi game had a great combat system with only two playble characters (I forget their names
). I don't know how you'd make an adventure game or RPG centered around a character who is known for racing towards a quick death constantly though.