If you've got the time, and you're at all interested in sours or Belgians, definitely hit Russian River. As previously noted, Lagunitas is on the way from SF, as are Marin and Moylan's, and, of course, wine country. The weather's also more reliably nice, because you're a little bit inland up there.
In SF itself, 21st Amendment and Thirsty Bear aren't bad, but aren't remarkable, either; same goes for Southern Pacific. I would say Speakeasy is the best brewery in San Francisco proper, at least that you have any chance of getting into; I have to reserve judgement on Anchor, because I haven't yet successfully gotten in. Magnolia and Social Kitchen are kinda hit-and-miss; they both tend to do a lot of weird styles, which are sometimes great but often "well, OK, I checked this off my list, don't ever need to order another one again." They're also both on the small side.
Drake's, while off the beaten path for sure, makes reliably excellent "standard" beers, and generally has somewhere between two and five one-off barrel-aged and/or sour beers on. However, unlike Russian River et al, the only other stuff out by their barrel house is warehouses and train tracks.
