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How often do you want to go where Delta flies (that's the only major carrier I know of with a deal with Amex - could be wrong though)? If you're only interested in domestic flights, there's no real wholes since their merger with Northwest. But if you want to go international, there will be a lot of places you just can't get to, even on partner airlines. The Carribbean, for instance, is dominated by Continental and American.
You should also see who those miles work, since they're probably not as simple as you may think.
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