We plan on traveling from Yosemite to San Simeon on a Thursday afternoon. Right now
we plan on being in the south part of Yosemite visiting the Mariposa Grove area in the morning and then heading out.
What is the quickest way out of the park and what are the best roads to take to get to San Simeon ?
Thanks

The south entrance is the best place to exit the park to go to San Simeon. Actually, the route is very simple. You exit Yosemite on Hwy 41 and follow that until you get to Hwy 46 just east of Paso Robles - take 46 to the ocean and head north on Hwy 1 for a little bit. When you go through Paso Robles, Hwy 46 and Hwy 101 are one and the same for a few miles.

About how long does this trip take? Thanks

I think mapquest would give you a decent time estimate. Most of the route is fairly straight 2-lane highway, 50-65 mph. From around Mariposa to Yosemite valley is much slower, tending to be around 30-40 mph.

I think there has been some major roadwork going on on the section of Hwy 41 between Kettleman City and Paso Robles, with significant delays and/or detours (especially 6pm to 6am).

Drive carefully on 46 and 41. They have the worst crash record in the state.
Be especially vigilant for speeding illegal passers who cause head on collisions.

Most of the highway has a barrier now, but some places still lack one.

I'm tired of taking care of traveling families mashed in their cars on those roads...