Well Iframes are useful if you do not wish to direct users away from the current page after they click on an NPC. Here's an example of how Clover used Iframes on her pokemon fansite:
http://www.sweetcharm.net/PokemonSit...useummain.html
Also I wonder how you make it possible for users to click on an NPC to speak with them. Mind explaining a little bit more of this?