The Pacific Coast Highway (Hwy 1) is the most scenic drive. It will be slow going, however, so give yourself plenty of time. The PCH tends to hug the oceanside cliffs and has many curves.
Start from Marin County or the Presidio (check out the historic sites, awesome views of the Golden Gate Bridge from the forest, and the Yoda statue in front of ILM's brand new headquarters -- the site's design itself was inspired by some work ILM did for Star Trek's "cadet academy").
Driving down the coast to San Diego you'll see: Half Moon Bay, Santa Cruz's Boardwalk Amusement Park, the 17 Mile Drive in Monterey, Carmel/Big Sur, Hearst Castle, Santa Barbara, and most of L.A.'s urban coastline/ports.
US 101 is a compromise route between speed and some interesting sites. Once you pass the dull suburban strip malls of the South Bay, you'll pass garlic capital Gilroy and have access to the Monterey Peninsula (if you veer off to Hwy 156). As the old Spanish road linking North and South, US 101 contains some interesting rural towns (Salinas, Paso Robles) on the way. And it shares a portion of Hwy 1's route along the Santa Barbara coast in SoCal before splitting up again.
Interstate 5 (via I-580) - The Golden State freeway is the fastest route from SF to SD no doubt, but it's also mind-numbingly dull, completely inland, and flat. Miles and miles of generic gas stations and dusty agricultural fields. If you're looking for a stimulating drive with lots to see, this isn't it.