San Simeon to San Francisco is the prettiest. You will be driving along the famous Big Sur - Coastal vistas the whole way, dizzying heights, and a few waterfalls (but you do have to get out and hike to see the waterfalls.)
Los Angeles to San Simeon is nice. You'll be passing thru Santa Barbara and the San Luis Obispo area. The coastal views south of Carpinteria, at Gaviota and at Shell Beach to Avila Beach are very picturesque. The highway 1 section to Lompoc and thru Guadalupe is interesting and nice but Big Sur is much nicer.
San Simeon to San Francisco would include Big Sur, which, hands down is the most impressive stretch of coastal highway in California, IMHO. As far as being the "prettiest," I'm not sure. Depends on your aesthetic. All I can tell you, is as a lifelong Californian, that when I saw this coastline for the first time, I was awestruck. It is, at the risk of using superalatives that are unfit for the task, magnificent.
Big Sur is, however, not a drive for "flat-landers" (as my father used to mutter under his breath, several cars behind, creeping excruciatingly slowly, for quarter-mile after quarter-mile). The impressive part of this coast line are the sheer drop-offs and windy nature of the road, coupled with the absolutely stunning views. Some drivers unaccustomed to this kind of driving have difficulty both managing the constant twists and turns and glimpsing the view. One visitor, in posting his trip report, specifically wrote about how the drive was horrible and unenjoyable.
In this situation, the view (for some, I emphasize) is white-knucle terrifying. It's always better to enjoy such by pulling over on one of the turnouts along the roadside, where you can take pictures, and let the relieved drivers behind you get on with their journey. California state vehicle codes require that drivers pull over to let others pass when the line gets to five cars or more. It's always courteous to pull over when there's far less than that.
I'd recommend Highway 1 from Santa Monica (just outside LA) to Ventura, and Highway 1 from San Luis Obispo to Half Moon Bay, just south of San Francisco. Currently, Highway 1 north of Half Moon Bay is closed, so you'll have to go on Highway 92 east to 280 or 101 north to get to San Francisco. However, if you go later in the year, Highway 1 north of Half Moon Bay might be reopened by then, so you can go all the way north to San Francisco on Highway 1. Check back later.
"a few waterfalls (but you do have to get out and hike to see the waterfalls.)"
Where would these falls be located, and how long is the hike?
The only one that I know is at Julia Pffeifer burns. but I am not the expert. This one you do get out, and take an easy 5 minute walk to see.
The waterfall at Julia Pfeiffer Burns State park is McWay Falls, there is another waterfall to the south at Salmon Creek, which is on the east (inland) side of the highway, it's tucked back in a canyon so you have to get out and walk a short distance to see it. There's also one at Pfeiffer Big Sur State Park, north of Julia Pfeiffer Burns, you have to do a short hike to see this one. These are the ones I've seen, the site below lists a couple of others too:
I'll probably just do the McWay falls. Too bad you can't get down to the beach there. But the view looks awesome, so I think I'll go for it anyway....