Unless you are talkin big game hunting ( and I mean BIG game) or for bear defence hot rodding the .45c is unnecessary. Just a good stiff load will do anything most of us ever need doing. IMO, that takes the differences of the Ruger frame sizes out of the equation and makes it a decision based completely on personal preference and feel.
But I would caution you against any SA (or revolver in general) without adjustable sights. 10 to 1 I prefer the looks of the fixed sight Vaquero, 10 to 1 I prefer shooting good adjustable sight guns. I'll sacrifice a little in looks for better shootability any day.
I run a wide range of loads in my guns, from mouse fart to full bore hunting loads and anything in between. You want to pick one or two loads and stick with them you may very well get by with traditional SA fixed sights but if you want to use that gun to it's full potential something better is not only needed but pretty much required.