I guess it all depends on what you are planning to do during your vacation.
1. Washington, DC - Museums are incredible and the public transportation make it extremely easy to get around. It's rather spendy, tho.
2. Chicago - Shopping on the Mile is any girl's dream. And a dinner cruise after a day of shopping is a great way to wind down. The "L" is ok, but taxis are a better bet for getting around. Not as spendy at DC.
3. To keep the kids happy, there is no place like the Orlando/Kissimmee area (Disney World, Universal Studios, Sea World and all the water parks). Rental cars are the best way to get around and the prices are reasonable. And beaches are about an hour away. Budget? What budget? :)
4. New Orleans - The food, the culture, the music. And a donkey trolly tour of historic French Quarter is a MUST. :) There are some very reasonable restaurants and hotels to be found as the city continues to rebuild.
I could go on and on but I'll let others answer. :)