Just stayed at the Park Hyatt, which is only a few blocks from Chinatown for $139/night for the weekend. Hyatt is offering great weekend deals, some of which include parking and breakfast throughout Winter. Location was perfect for us, getting some nice exercise walking to the Wharf. If pressed for time, Muni's F Line runs right along the Embarcadero.

We also drove up along Hwy 1 from LA to SF last month. I also agree that weather is a huge factor. If good, I'd suggest allowing two days & staying overnight somewhere along the way like Cambria (on the Central Coast just north of San Luis Obispo).