How can it be a true sequel, if it doesn't at least revisit the setting of the original game? It doesn't have to be the same cities and areas, but having a Titan Quest game, without a Greece, is not Titan Quest. But, where can they possibly go at this point? There are many mythologies in the history of our world, but most of them are not distinctive enough for a unique game setting... The only place they can take a sequel, or a new expansion to is the ancient Aztec and Mayan civilizations and maybe India...Also, maybe Rome?
And let's have a real Tartarus act, this time with a story and quests, so we can forget about that arena abomination in the TQ AE.