Originally Posted by
DELee
The Santa Fe depot downtown is more current urban, next to various piers and San Diego Bay. It is much more spread out but there's far more there - a few blocks north is Little Italy, going east you'll hit Horton Plaza and its mall, heading south is Seaport Village and the Marina, taking the trolley Southeast, you'll be between the Convention Center and the Gaslamp District.
Something to note as well is that Horton Plaza has seriously gone downhill in the last couple of years, so it might not be worth the visit unless you're into dead malls. Everything else is spot on though.