It takes about two hours to drive to Mexicali [1] from the San Diego airport. Once you’ve arrived, you could spend just an afternoon and evening getting oriented and preparing for a trip to San Felipe [2], or a couple of days to explore the city’s few attractions.
The most popular weekend itinerary in this area is a trip from Mexicali to San Felipe and back (two hours by car each way).
With a week or more, you could add a side trip to the Cañon de Guadalupe [3], and continue south of San Felipe to Puertecitos. With a four-wheel-drive vehicle, you could turn this trip into a loop, following the coastal road all the way to Gonzaga Bay [4] and heading inland to meet the Transpeninsular Highway at Chapala. From there, you can head south to Bahía de los Angeles [5] or turn north to Ensenada [6] and Mexico 3, which returns to Mexicali.
Links:
[1] http://www.moon.com/destinations/baja-cabo/mexicali-san-felipe/mexicali
[2] http://www.moon.com/destinations/baja-cabo/mexicali-san-felipe/san-felipe
[3] http://www.moon.com/destinations/baja-cabo/mexicali-san-felipe/mexicali-tecate/canon-de-guadalupe
[4] http://www.moon.com/destinations/baja-cabo/mexicali-san-felipe/san-felipe/near-san-felipe/punta-bufeo-punta-pinal
[5] http://www.moon.com/destinations/baja-cabo/baja-s-central-desert/bahia-de-los-angeles
[6] http://www.moon.com/destinations/baja-cabo/ensenada-el-rosario/ensenada