So a few my suggestions for travellers with a lot of energy hehe:
1. FOR A FEW HOURS VISITORS (longer lay-over or busy business trip or...):
- Gaslamp District especially but NOT only in the evenings (easy and fast access from the airport): walking, eating, shopping in nearby Horton Plaza,
- Old Town District,
- Heritage Park,
- Villa Montezuma,
- Coronado Island (by ferry).
How long does it takes? Minimum a few hours with dining.
Or in summertime one from the first above suggestions + BEACH (the best is in Coronado Island) hehe!
2. FOR 1 FULL DAY VISITORS:
I would try to add to the above suggestion either ZOO (at least a few hours) or Balboa Park (even a full day maybe not enough if you wish to visit all museums)
3. 2 DAYS
Look at point 1 + ZOO + Balboa Park
4. 3-4 DAYS
Like in point 3 + trip to Mexico (Tijuana) or/and Point Lloma, La Jolla, San Diego ZOO's Wild Animal Park, Anza-Borego Desert State Park + SeaWorld (hmm... 1 full day).
WARNING: If you have not so much energy - multiple the above times at least by 2 hehe!
.VT-er Linda (lmqluque) :-))))))))))).


