I've driven 54 by Lake Cachuma lots of time but have never ridden it. So no comment. But I live on Morro Bay and have some experience with west/east routes around here. I would not ride Highway 41 between Morro Bay and Atascadero. There are no shoulders for much of it, steep rock faces on one side, lots of turns, and lots of traffic - people in a hurry. No thanks. Highway 46 between Highway 1 (south of Cambria) and Paso Robles is a very bike-friendly road. There's a nice shoulder the whole way. It's a long climb, but not too steep.
There are a couple of alternatives but they take you on dirt roads. One is Santa Rita Creek Road. From the west side you leave Highway 1 in Cayucos on Old Creek Road. There's a good climb, then a long downhill by the reservoir. At the bottom there's a right turn onto Santa Rita Creek Road. This becomes a dirt/gravel road and goes all the way over the mountains to the east side. It comes out on Vineyard Drive, just across Highway 101 from Templeton (which is north of Atascadero and south of Paso Robles.)
Another way to get from San Luis Obispo over the Cuesta Grade to Atascadero is via Stagecoach Road. They've made some changes since the last time I rode this route a couple of years ago, so you might want to check with a local bike shop or someone from the San Luis Obispo Bike Club (
www.slobc.org) before you go. The way it used to go, you'd get onto Highway 101 at the end of Monterey Street, ride on the northbound shoulder (plenty of room), then cross over both lanes of the freeway when you got to the turnoff (left) to Stagecoach Road. (Be careful!) I've heard there's an underpass there now, but I'm not sure. Stagecoach is a dirt/gravel road that goes almost to the top of the grade. The last time I was there you continued on the west side of 101 down a surface road next to the freeway. When you got to the bottom where it deadends, there's a trail off to the left that takes you back to the southbound shoulder of 101. I couldn't find it the last time; it came out behind a bush and it was camouflaged as if someone didn't want you to find it. As I looked around, some riders came out from behind the bush, revealing the entrance to the trail. The trail was short and dumped me back onto the southbound shoulder (I was going northbound.) I stayed on that for maybe 1/4 mile until I came to a place where you could cross the freeway. After you cross you stay on the northbound shoulder until the first exit - the Santa Margarita exit. Take that to the right and the road you'll be on becomes El Camino Real, which goes from Santa Margarita all the way to the north end of Atascadero.
I hope that helps.