Whats most important is making sure that you train your muscle memory one way, and that way works on all of your defensive guns.
For example, I usually carry a 1911, which is the platform I am most comfortable with. My grip has the firing thumb resting on the safety, with my support hand thumb over top of the firing thumb, so the safety comes off when I grip the pistol. My other carry guns are a xD subcompact and a P3AT, and with the same grip there are no problems. I have a Stoeger Cougar, which is my fiance's nightstand gun. Even though it has the Beretta-style controls, which are opposite from the 1911's, it sits with a round in the chamber, safety off, decocked (hammer down). The slide mounted safety is so high that my thumb doesn't hit it when I go to swipe of a 1911 safety, so there are no issues.
You don't need to go out and buy all Glocks or all 1911s for defensive handguns. Train one way, then make sure the guns you have all work in that way. Most will, with some exceptions. Even though I like some HK handguns, the funky magazine release turns me off of them for defensive use.