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I think one day, dare I say, like the Ap*calypse saga in the X-M*n (don't assassinate me!), there will be a greater evil that will try and rule both areas (The Rogue Isles & Paragon City) and both good and evil will have the chance to team up and beat the sh*t out of them.
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I think that would be a sweet idea...maybe even something along the lines of a "Hive" type zone with something much tougher to beat than Hami!!