What I could see happening is alot of old areas get filled up, such as the remnants of Orr and all that desert and northern Ascalon. You can cram so much into there.
Also if you think about new quests have been added to old regions so why is it that new quests and missions cannot be added to new regions. Think of The Great Wall mission, and say in two - three expansions you can go there and lead a battle all the way up into the north lands, all this could be done by simply adding special expansion with/without districts to an area.
Then again super mapping in GW makes size... really small :P
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