Some major differences that will distinguish Guild Wars 2 from the original is less instancing making the world more persistent with improved freedom of control to move (jump!) around and explore; a higher level cap as the original is capped at level 20, there might even be no level cap; a realm-versus-realm like PvP system. To get all these features in Guild Wars the game would have to be radically altered -- a sequel is the best solution opposite to a "new game experience" that would only end up butchering the original Guild Wars. After mulling over the list, everything proposed looks outstanding. I'm definitely more excited about Guild Wars 2 than Guild Wars, I would love playing a Guild Wars game that was more like a MMORPG with no monthly subscription cost. You heard me right, no monthly subscription cost for a MMORPG.
Guild Wars 2 takes place roughly 250 years after the Eye of the North expansion, presumably the last Guild Wars expansion pack. The Guild Wars 2 open beta is currently scheduled sometime for the 2nd half of 2008.