I know this is considered VERY far out, but given the series has done time travel, multidimensional travel, Kaiju, Nightmare on Elm Street and had you riding a Dragon to space to fight a meteor surfing alien, I don't think it's THAT far out in comparison.
How about a region completely different, something truly alien for the series, think 300 year jump into the future on their world's equivilant of the Moons of Jupiter (aka the classical 4, Io, Callisto, Ganymede and Europa), half terraformed. A mixture of classic Pokemon and truly alien Pokemon like Deoxys was. The ability to play as different races like human, a space elf like race (the offspring of humans and...) and Douhel, a non-pokemon distint cousins of Deoxys.
Now to me, that would get me excited to play a new Pokemon game and something truly unique for the franchise.