I agree that 296 like a magnum primer. For the low velocities you are talking about, I would stay away from 296 and go with a flake powder like 2400 or similar. With a magnum primer and 296 you can get some real horsepower out of the lil 45. I've tried bullets up to 405gns in mine, but think that 350 is a reasonable max bullet weight. Hodgdon's has load data for a 360gn cast useing H110 if your interested. I have a Houge monogrip on my 4 5/8" blackhawk and like it much better than the pachmyers.

I'm shooting exactly the same gun you are, using 300gr bullets and it is accurate! My load is a heavy charge of 2400 behind the Hornady bullet and it works. I pulled the factory stocks off my Ruger and went to a set of Pachmayr's and this seemed to make a difference in how I could hold the gun - I do have very large hands.
If I were you I would definately start trying a variety of load combinations. As someone remarked above (Atkinson?), few guns will shoot well with all loads and all bullet weights. In fact, I'm working with a Ruger 77MkII in 7x57 right now that really shoots well with light bullets but have not found "the" load for anything heavier than 160gr. Anyone have any help here????

Sounds like you're getting some kind of recoil effect on your wrist. The only way to really tell is with a Ransom machine rest but they are costly.

W296/H110 powder likes magnum primers so that may be the source of the problem there.

I've been using Blue Dot and Universal in my .45 Colt loads but with heavier bullets (270 & 310). With the 270 Keith from Leadhead, I use 13.5 grains of Blue Dot and get about 1050 from my Bisley. Accuracy is good and fired cases drop freely from the cylinder.

As it turns out a bit more patience and your advice worked.
I started by re-working the powders I had used. Unique went accurate at 10 grains (just.5 grains more). TightGroup, I had to go down from 9.5 to 8.4 grains. Also tried Lil Gun which works the best of all at 18 grains. However, W296 produced some wierd results. Squib loads, even at listed max, just 400 to 600 fps (that's not a typo!)And particularly dirty. It was chilly, 23 degrees F, during the time I chroned them and shooting at an agle of 15 degrees down.(Chron was working).
All of the magic loads had one thing in common: between 1000 and 1100 fps. Anything over 1100 started going left.