San Francisco down to San Diego via the coast is a good drive. There's some good tips on San Fran to LA on this discussion here: http://travellr.com/questions/united-states/306/what-are-some-of-the-best-things-to-see-along-the-coast-road-from-san-francisco-to-la almost 9 years ago
I agree that the Pacific Coast drive mentioned above is beautiful, but you may be looking to get a bigger slice of the pie than just California.
There are 3 major coast to coast interstate routes that you can take - a more northern one (I-90, start Seattle,Wa finish Boston,Mass), a middle one (I-80 start San Francisco,Ca finish New Jersey) and a more southern one (I-10 start Santa Monica/Los Angeles,Ca finish Jacksonville, Florida).
There is a really good website detailing US interstates here - http://www.interstate-guide.com/index.html
Or of course you could do the traditional Route 66 - from Los Angeles,Ca to Chicago,IL
Whatever you choose Good Luck!!! I personally would love to try going from coast to coast along the Southern States - it would be a really interesting experience with lots of variety. And if you opt out of driving - try taking a train from California to Colorado - lots of pretty mountains to ride through! almost 9 years ago