I like DC, Boston and NYC for the big cities, probably mostly because I know them the best. I feel like you have to go to a big city a few times to find the real great spots. I've never really got San Fran, but maybe just haven't been enough. San Diego is great, but not for the city experience.
I'd pick a lot of smaller south east cities actually as my favorite weekend trips. Charleston, SC has so much going for it. Richmond, VA has so many great restaurants and breweries now.
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