As a pedestrian, I've done San Ysidro a few times, and Otay Mesa once. Whereas the latter is much less busy than the former, it's also in an area where you're much less likely to end up as a day-tripper.

Also, from Otay Mesa, if you wanted to do the public transit thing, then you'd have to take a bus to the (Iris Avenue) light rail station, whereas from San Ysidro, you're already at the light rail.