Since you're implying they have 2 days to make the trip, they will have plenty of time. Be aware that tourist spots will be busy since it's Spring Break for many schoolkids and families are taking local vacations with the sour economy.

From MRY, she can take Highway 1 which hugs the coastal cliffs down to San Luis Obispo. It's one of the world's most spectacular coastal drives. A stop at Hearst Castle is worthwhile. It takes 4-5 hours to drive the 125 miles especially if caught behind a big RV (caravan) that refuses to yield to let others pass. The road is very winding (many curves posted for 15mph) and southbound she will be on the ocean side of the road with 300m sheer dropoffs on the right side. But if the driver is confident with that as well as driving on the right, then it's no problem.

The other alternative from MRY to SLO is US101 which is inland. It's scenic through rolling hills and farmland. Allow 2-3 hours since it's interstate-grade divided freeway.

If they need a basic, clean place to stay, either Motel6 in SLO is adequate. I slightly prefer the "south" one to the "north" (they are 2 blocks apart). Another suggestion is Solvang; I like the Solvang Inn and Cottages. The town is a Danish settlement and everything in town is Danish-themed. Many small shops, galleries, antique stores, etc. The movie "Sideways" was filmed in the area.

Curious why Madonna Inn is off her list- simply because she has already been there, or was there a bad experience?