In general I would not advocate carrying a handgun with the manual safety on. If you find yourself in a sticky situation, you want to be able to draw and fire quickly. Turning the safety off takes time. Perhaps only a split second, but you could lose your life in a split second.
I think the best way to carry is decocked with a round in the chamber. The P99 AS, for example, has four internal safeties and a decocker that, when pressed, puts it into a heavy 11 pound DA trigger pull. It has no manual safety, but I think that's unnecessary. The gun will absolutely not go off unless you pull the trigger, and there's nothing in your holster or your pants that can pull the trigger with even a half pound of force, much less 11 pounds.