I've always thought it would be cool to run an In Nomine game set during a different time period. I had a friend in high school try out a one shot In Nomine set in the wild west, a la Deadlands. I played an Ofanim Gunslinger who hunted down Demons. It was a good time.
Or Middle Ages. That'd be crazy too.
Or even during Uriel's Purity Crusade. Fight off Dragons, Chimera and other Ethereals.