I've done the San Diego/Puerto Penasco drive a number of times over the years and have always traveled through the San Luis POE just south of Yuma, which takes about 6 hours door-to-door. The San Luis border is currently open 24 hours and there is an excellent toll road south of San Luis that goes directly to El Doctor, a little northwest of El Golfo and connects to the coastal highway to Puerto Penasco. The coastal highway along that stretch is very pretty and desolate, with sand dunes that often blow onto the road. I've never taken the route through Mexicali to the Calexico border, which may save you a few minutes but also keeps you on Mexican roads for more of your trip. There are others on this forum who travel that route often may help with more intel and suggestions.