I actually think it would be quite interesting if they did a late 19th/20th century Total War. I think it would still be original because TW games combine the real-time strategy elements in fighting battles as well as turned based modes typical in civ sims. Plus, they couldn't confine themselves to the WW2 era.
You could start the game off in 1871, when Germany was unified, and have USA, Germany the British Empire and Russia as the first playable factions, and the game lasts until, say, 1991 or 2000. The most interesting thing about it i think would be playing through a familiar time period and having a completely different set of events occur so the game by the finish looks very different to what we are familiar with today. Things like aircraft would add some new and interesting game play features, as well as nuclear weapons and more radical political ideologies.