I love North Beach and all the Italian Restaurants on Columbus St. You can sit out on the sidewalk with a bottle of wine and a nice plate and just people watch. Calzones probably has the best atmosphere for that sort of thing.
I agree with the general sentiment to avoid the wharf. Fisherman's Grotto is pretty good. Sinbads is on Pier 2 in the Embarcadero and has good food and is right on the water so you get a nice view of the Bay Bridge, Oakland, etc...
peter12 is right - the Mission and Mexican food is wicked. Taqueria Le Cumbre in the mission has great burritos and is super famous in the area. Ike's place near the mission has really unique sandwiches.
La Trappe on Columbus St and Greenwich is a really cool spot. Very limited and unique menu but the beer menu is pretty much a novel... at least 60+ pages.
If it's a clear day, go to the top of the Mariott and their skylounge. Very cool views, but only stay for a drink and be prepared to pay $15 per drink.
There are some really cool Tapas restaurants in and around North Beach and the financial district: Illuna Basque on Union St. just off of Columbus. I can't remember the other one, but if I remember...
You really can't go wrong though. LOTS of wonderful restaurants. If you want more local advice, feel free to PM.
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