The #1 issue is proximity to population. Obviously the East Coast is the place. As much as I'd love for it to be in Seattle (GenCon's home town no less) or even California you won't get anywhere near as many of the car travelers to come even if all the current West Coast non-attendees started going. The East Coast sits at around 38% of the US population and the West Coast around 16% (gulf coast is about 12%). The East Coast is also easier to fly into from Europe and while that's not a huge number it is more than the rest of parts of the world. End result, if it left the East Coast it would almost be a guaranteed drop in attendance.
The #2 issue is finding a venue that has the space. You need to be able to reasonably walk from one event to another within say, 10mins time or so. Just GenCon's merchant room is over 200,000 sq ft (about 3 1/2 football fields), which is packed (and some companies choose to use a separate room). The convention center has 1.3M sq ft, although I believe that includes the stadium, which has not been used yet (it's under 190,000 sq feet though).
The #3 issue is finding a VERY large number of hotel rooms within a reasonable distance. I'm just going to say, within 8 blocks. There are venues that have more closer, but the outer perimeter may not and you have to find this after you find a convention center big enough.
The #4 issue is the local unions. This is more of a cost issue and a dislike of the gaming companies to not be able to handle their own logistics. A few locations that would work have been shot down because the labor has to be done by local workers due to unions. So you aren't allowed to do your own setup and tear-down, you have to use the local labor (which costs).
Now, #1 through #3 have some possibilities... but #4 comes down to a question of additional cost. So, it might come down to is GenCon willing and able to pay for their stance?