When are you coming? If it's less than 2 weeks from now, you're probably out of luck with Slanted Door reservations, though you can do walk-in with varying sucess, depending on your flexibility. We just got a Friday night table for 3 with a 5-minute wait a few weeks ago. Of course, they needed us to be out in 90 minutes but the service was so efficient that wasn't an issue. For a first-time visit, try the classic dishes like the shaking beef and the imperial rolls.
For the others, you can choose between quintessentially "San Francisco" experiences, and newer places doing more innovative things with good food.
Another factor is where you're coming from. For example, if you're an LA denizen some concepts here will seem tired while a New Yorker might pooh-pooh the pizzas we rave about at Delfina La Ciccia or A16.
Myth is terrific - not too formal, not too expensive, "but just right." However, I wouldn't classify it as a unique destination.
Iconic places include Aqua, Boulevard, Acquerello, Delfina and Gary Danko. More innovative and unusual places include Ame, Michael Mina, Frisson & Winterland. Town Hall fits somewhere in between, having rapidly graduated from newest culinary darling to culinary stalwart in a few short years.
You can also let availability determine your "eat-tinerary". opentable.com does reservations for most of these places, so check it out: http://www.opentable.com/rest_list.as...
Enjoy your trip!
Consider some of the places in North Beach. Osteria del Forno is a wonderful experience, if not haute cuisine. Arrive early and expect to wait outside on the sidewalk because no reservations are taken. Rose Pistola, also in North Beach, is seriously good and you definitely can make reservations there. Check the SF Chronicle at SFGate.com for current reviews and a list of the top 100 restaurants in the City and surround areas, in addition to another list of the 100 best budget restaurants. Both lists are in the food section of the paper, and Michael Bauer, the food critic, has a staff of writers bigger than the population of some countries--they take food very seriously.
You've got a ton of options, and it is hard to go wrong.
If you want to check out some of the top places, here's an article from last fall on the top 7: http://sfgate.com/cgi-bin/article.cgi...
Since then, Myth and Manresa have received a lot of good press on these boards, and Fifth Floor a bit of bad press.
I would add Tadich Grill for perhaps lunch, great old SF place. Myth is hot and very good. Had a wonderful meal at Ame Friday night. Boulevard is lovely with great food and service plus a great view of the bay.
Luella, Rue Saint Jacque are great little neighborhood places both with great food.
Have fun, report back.