I vote for the .45 Colt - - -
- - - for sure, if you handload. Actually, nowadays there are a lot of reduced power "Cowboy action shooting" loads available. And a growing number of various other loads available, even without having to go to the auxillary, .45 ACP cylinder. (Wow! I didn't know that option was available. I may just have to - - - No, I can't afford it. Already have a DA .45 Colt. )
And, anyway, the short-case Scofield loads are very mild to shoot.
And if you DO handload, the whole field is open to you! Middle of the road loads, like a 255 SWC at around 800 fps, for everyday use. Same weight bullets in RNFP down around 700 fps for Cowboy matches. The .45 S&W (Scofield) cases, with 230 RNL around 600--650 fps. These can really be pretty economical.
And, this being a STRONG, MODERN revolver, you can load up cartridges fit for medium-to-large game hunting. You can get 300-gr-plus bullets and load up some for protection in bear country.
About the only thing nearly so versatile is the .44 mag, and I believe they sell it with an optional .44-40 cylinder. This one dates from the same year of inception as the .45 Colt, 1873. And you could load up the (1905-era) .44 Special in a wide selection of power levels, before you get into the hefalump defense level .44 mags.
Say what you will about Ruger's political outlook, they sure have a nifty product line in the Vaquero revolvers!
Best,
Johnny