As someone who drives 101 from Northern CA to Southern CA regularly, there are a few easy stops along the way. If you need a bathroom break, King City is the easiest stop. That's probably about 2+ hours into your drive. You can take the Broadway exit and stop at either McDonalds or Starbucks, getting back on the freeway is easy as the onramp is next to the off ramp. If you can continue and don't need a break or snack, there is a rest stop between King City and Paso Robles (probably another 45 minutes). It has an easy entrance/exit and the bathrooms are always clean.
A fun place to stop for food is Madonna Inn, located in SLO. This has a decent exit/entrance to the freeway. The Cooper Cafe is decent food but the surroundings are pretty and fun to look at. Depending on how fast you drive, that's probably about 3+ hours of driving.
As someone mentioned above, Split Pea Anderson is a good stop. It's really good if you need a bathroom break and want some free crackers & cheese. If you park in the back, you can go in through the side entrance, run to the bathroom, grab your free crackers/cheese and then head back to your car. Easy access to freeway. Can you tell I've done this before.
Ventura would be another good spot, that's probably 5+ hours of driving. If you like burritos, stop at Corrales Mexican Food and get a 3-way. Unfortunately, this is not a quick on and off from the freeway but worth the short trip. The restaurant is located on Thompson Blvd., you need to take the Seacliff exit (there are a two Corrales restaurants in VTA, this one is better).
The only other stop I can suggest as you get further down into LA is Olvera Street. Kinda kitchsy but it's fun to stop and maybe grab some delicious taquitos. It's located off of 101 and has a decent off/on ramp to freeway.
Unfortunately, I don't stop much after LA. I don't know the areas that well and I always worry that I'm gonna stop somewhere crazy and unfamiliar.