We had a lot of fun doing the wine tasting route in Napa (stay at a bed & breakfast, it'll be worth it!) Second bit of advice is to hire a taxi/limo (if more than one person, it's not that bad, esp when you consider a DUI). We were there for three days, and wished we had one more day.
Provincetown, Mass was a lot of fun when we were there. Just seemed like it was a really good mix of people.
Las Vegas has been fun. We've stayed at the Venetian. We like that because it's a comfortable room to just relax in.
DC has a whole bunch of museums to get lost in, and a very active nightlife.
Portland, OR is my second-favorite city on the West Coast, and is a really relaxing time. My favorite goes to Vancouver, B.C. It's incredibly vibrant.
Bottom line is what you're into doing. Camping/hiking/outdoors? Culture/theatre/eating out? Meeting people?
Whatever you do, have fun!