Don, make sure you get good input from a local person on travel time to La Jolla at the time your wife will be traveling. During high traffic periods it has taken me 30 min to get from one location to another, both in La Jolla. Our SD Townhouse is on the Embarcadero in the city, a block north of Seaport Village. It takes 10 to 15 minutes to get to the Rt52 LaJolla exit off the 5 freeway. From that exit to Prospect street is at least 15 min, sometimes 25 min at high traffic times. It is only 3 miles. Said another way, I can get all the way to the Palomar Airport exit in Carlsbad in the same amount of time it takes to get to a parking garage on Prospect street in LaJolla.
If you select a home in a community that has an HOA make sure you look at the CC&R's closely. Some of these HOA's have very restrictive rules about street parking and leaving vehicles in driveways. Homeowners use offsite storage or PODS service because of lack of storage space. Many two story tract homes in built in the 70's and 80's have a bonus room above the garage that functions like a basement. It was popular then to put pool tables in them.
Our house was built with two masters, we removed the closet to maximize the room size.
Back to your question about layouts in garages. There are many operators who have successfully put their layout in the garage in SoCal. Like some have pointed out, there are a lot of inland locations, generally 5 or more miles from the coast, that see 100deg daytime highs. Layouts usually do not care but the operator might. Garages here are different than where you now live. Any garage attached to the house will be vented. It is a code requirement and the hot water heater will be in the garage. My garage is just under 700 sqft and has about 5 sqft of vent area. This means there will be some dust infiltration and it is a bit harder to control the temperature. Detached garages almost always are vented as well, but a few local codes allowed them to be unvented. I believe any newer detached garages must be vented.
There are a lot of arbitrary rules for lot usage out here, but some communities have almost none. Granny Flats now must be allowed regardless of zoning but the setbacks and lot coverage ratios still apply. The reality is it is now easier to convert a garage to a rental unit but still just as hard to add a separate structure unless the lot is large.