I think it would be interesting to build a game like EVE which maps the management of spaceships and cargo to the management of real world businesses like a toilet seat manufacturer in Iowa.

While users of the game are creating distribution networks and building custom ERP solutions they would really be managing businesses (without their direct knowledge). If you were really successful in the game then you would find yourself managing the logistics of a much larger real world company.

I guess the challenge would be to create game mechanics that mapped in a way to real world business constraints that made sense.