My Cowboy Action load has proven consistently accurate in a wide variety of different 45s, and is my generic go-to. I use a bullet cast from a Lee 255 grain RNFP mould, lubed with Alox, and 6.0 grains of Titegroup. Groups under 2" from every handgun I've tried it from (USFA, Colt, Ruger, Cimmaron) and does great from both Marlin and Rossi leverguns. Handgun groups range from bragging-size to 2 inch at 25 yards, and the carbines/rifles from cloverleafs (Rossi) to a little over an inch (Marlin) at the same distance. I've popped jackrabbits at 200 yards with the 20" Rossi 92, and hit ram silhouette targets at 385 yards with the Vaquero, so it works for long range, too.
The Lee bullet has a flat base and I cast it soft enough that I can cut it with a fingernail. No leading and just a superb performer. I have never gotten anywhere close to the accuracy with hard-cast bevel-base/crayon-lubed bullets, and leading has been evident with that kind of slug. If one doesn't cast, Desperado and Rimrock bullet companies offer high-quality softer bullets.
Velocity is just right at 800 FPS from my 5 1/2" Vaquero. I have gotten slightly smaller groups from a couple guns using 5.5 grains, but since it was not as accurate in the others and the difference was small, I settled on the 6 grain load as "universal". I would recommend loading 5.5 up to 6.0 and seeing which is best. Titegroup is not position sensitive, so it makes a great economical choice for loading those big cases while still delivering consistent velocities regardless of if the powder is up near the bullet or back near the primer. The drawback? It is possible to double-charge, so- as with all handloading- attention must be paid.