I really like driving up Highway 128 - lots of wineries on that road, it's more off-the-beaten-track than many winery areas, and it's a very pretty drive. Along that road is the town of Boonville, which has a really nice little microbrewery/restaurant, and some interesting history (they have their own language, Boont).
If you go to the end of it, you hit Highway 1 along the coast, which is a stunning (though very very curvy) drive. A few miles north is the town of Mendocino, which is very charming. Surrounded on 3 sides by park land, cliffs and crashing ocean waves, and a very cute row of shops and galleries.
Highway 128 can be accessed by going north from San Francisco on Highway 101 and getting off at Cloverdale (about an hour and a half north). The drive along 128 and 1 up to Mendocino is about 2 hours if you go straight through.