You might find this thread helpful: San Fransisco to San Diego - In My Humble Opinion - Straight Dope Message Board
I agree with the general sentiment of making it a one-way trip. If you can afford or avoid the drop-off fee on the car rental, I would fly into SD, drive to SF, and fly home from there.
I can tell you a bit about the drive from Cambria to Monterey, having done it last Friday with my family. The most important thing is: don’t miss it! It really is very beautiful. Right now there are masses of wildflowers blooming everywhere, making it especially nice.
Cambria is a nice place to stay, or at least make a stop. There are lots of little motels, places to eat, and a very nice walkway overlooking Moonstone Beach.
Hearst Castle is one of those touristy places that are actually worth visiting. It really is something! Other things to see: the elephant seals at Piedras Blancas, McWay Falls, Pfeiffer Beach, Point Lobos.
It might be easier to pull over to gawk at the scenery if you’re southbound, but there are plenty of places on that side of the road that are big enough and safe enough to pull into even if you’re northbound.
Allow a lot of time for the traffic, driving carefully on the winding road, and stopping to look at the scenery. If you have the time, spend a whole day going from, say, Cambria to Carmel or Monterey, stay the night, and then go the rest of the way to SF on day two. Possibilities for the second day include spending some time in Carmel, and maybe checking out Santa Cruz.
Bring sweatshirts and/or windbreakers, as it can be cool and very windy.
We also stayed in SF on this trip, in a very reasonably priced motel with free parking. As it turned out, we used public transportation a lot, but we also found it useful to have the car. We drove down the Crookedest Street (part of Lombard), and to Muir Woods, and to Golden Gate Park, and to the nearest supermarket; we took buses to the Ferry Building, Fishermans Wharf, Coit Tower, and Chinatown. A bus/trolley ride is only $2, and your ticket is good for transfers for a few hours.
On preview, I see you’re planning a two-week trip. That’s good - it should give you time to check out both cities and take your time driving between them. I hope you have a wonderful trip!