Zuni Cafe is a San Francisco institution. I don't want to oversell it, but few places offer a better cross-section of the city than Zuni. In fact, it's one of those places that out-of-towner foodies make a point to visit.
Zuni has been on Michael Bauer's Top 100 list for the past seven years and who knows how long before that. I wouldn't consider the place innovative, but they do everything extremely well.
Zuni is most famous for its roast chicken for two, which comes with bread salad. Warning: the bird takes an hour to cook, so if you're going to order it, tell your server immediately after you're seated. The hamburger comes on grilled focaccia and looks more like a sandwich than a burger, but it's also worth a trip.