2 months ago I would have recommended two: Hyatt for big cities and Marriott to "fill in the gaps".

Since Hyatt has just devalued all of their outstanding points by about 30%, I can no longer recommend it as a first choice, even as a diamond member.

I have heard nothing but great things about Starwood, so perhaps a Starwood/Marriott focus might be better.

Hilton is worthless - between the dozens of rates, some which qualify for double points, some which don't, and the fact that they owe me 40,000 points and won't look into it, I wouldn't recommend that dog at all.

Marriott also gives you the opportunity to buy heavily discounted gift certificates, which is a super plus in my (check)book. They also have a guarantee that if you are elite and do not get the room you requested, they have to pay you big $$$. I have yet to try out this feature.