Part of it is purely design dictated by the fact that you don't have much choice of where to put the notch on a 6-shot gun.
If you look at the cylinder in a 6-shot, you'll notice that each chamber is directly opposite the one on the other side of the cylinder. That's because each chamber is at a 60 degrees angle from the centerline of the cylinder. Three 60-degree segments is 180 degrees, or 1/2 of a circle.
On a 5-shot pistol, each chamber is at a 72 degree angle from the centerline of the cylinder, meaning that when the top chamber is lined up with the bore, the two chambers on the bottom are offset from the centerline of the cylinder. That pretty much guarantees that the notches are offset from the center of the chamber.
In order to put the locking notch between the chambers, you have to offset the location of the locking bolt in the bottom of the frame. Since that area isn't all that wide, it's a bit harder, but not impossible to do mechanically.
I hope I've explained this adequately, as I was finding it hard to describe so that I could understand what I was saying.