Can't answer w/o knowing when the trip is. Makes a huge difference re where you can and can't drive.

Oops sorry - we will be leaving Sanfrancisco at the end of Feb this year! dates not confirmed yet but around last week of Feb/early March.

Are some roads closed due to cold weather?

If it was summertime, no question most of us would say Yosemite.
I doubt that you can get there in February.
How about driving south along the coast as far as Cambria?
Take route 46 east all the way to Rt. 99 then south into Bakersfield and Rt. 58 over Tehachipi Pass to get to Barstow and Interstate 15 to Las Vegas.

Do as tomfuller suggests if you haven't already done the coast drive on the way up from LA. Otherwise, there isn't anywhere along the main routes to LV that are stopover worthy. You could loop over to Yosemite, take a peek,and continue south thru Fresno to Get back to Hwy 99, but it would depend on weather and finding accommodations. You may be better off just driving the 10 hours straight to LV.

As MichelleY says (if you have already done the coast road) there is no advantage to stopping anywhere between SF and LV. None.

But where are you going after Vegas? Is that the end of your trip? If so, consider dropping your car in San Francisco and flying to Las Vegas. It will save you HOURS of tedious driving. Plus driving down the central Valley in Feb can be so foggy it is dangerous. There are cheap airfares SF on Southwest which is a terrific airline but doesn't show up on kayak/orbitz/etc.

Even IF you are using a car after LV, you might even consider dropping the first car in SF and collecting a 2nd rental when leaving LV.

I agree with both janisj and MichelleY. If you have already traveled the coast, just go down I-5 and cross over to Rt. 99 wherever you want to to get on Rt. 58 at the south end of Bakersfield. If you are very tired, the only place I would stop for the night would be Primm Nevada at Exit 1. (42 miles from LV). Buffalo Bill's is not as nice as Las Vegas but it is better than getting lost in LV on your way to a hotel.
The other thing I just found is that Allegiant airline flies to LV from Monterey on Sunday Wednesday and Friday in the afternoon. http://www2.allegiantair.com/
The fares are cheap but they do charge for carry on baggage as well as the checked baggage.

If you do decide to fly, car rentals in Vegas are pretty cheap, so are hotel rooms.

One less frequently used website I use is www.cheapovegas.com

If you've done the coast and would like to see Yosemite, take I-80 out of the Bay area over to Placerville, wind your way down SR 49 through the Gold Rush country and take SR 120 into Yosemite, drive to the Valley, do a drive through then exit on SR 41 into Fresno. At that point you'll probably be ready to stop forthe night. Next day SR 99 to Bakersfield, SR 58 to Barstow and I-15 into LV.

But, if you haven't driven Highway 1 on the coast, do that instead as far as Cambria or Morro Bay before cutting inland.

Just a comment. Any way you can start out in SF, then drive to LA? Las Vegas is only a 4 hour drive from LA, but to get there from SF you will have to drive south again after having driven north to SF and there is nowhere worth stopping unless you can get to Yosemite.