When people say they have a Mark III 22/45, I still sometimes wonder what gun they have. Maybe they are talking about a newer 22/45? The Mark III and 22/45 are very different guns when it comes to ergonomics.
The Mark III:
-Feel a lot better to me. Fits my hand better and points better.
-Are a lot heavier than the 22/45
-Have a different grip angle than the 22/45
-The bottom plate of the magazine is even different than the 22/45. You can't use a Mark III magazine in a 22/45 without switching this.
I prefer the Mark III by a lot.