I've got a .45 LC "New" Vaquero with a 4-3/4" barrel as well as one of the Lipsey's .44 Specials in the same length, and a 50th Anniversary .357 Flat Top. It's no surprise that the better sight picture offered by the adjustable sights helps in shooting accurately.
Given that each of these handguns has its own accuracy potential, regardless of the sights, I find that the open notch type on the Vaquero costs me about 1/2" at 25 yds. It will still shoot 2" gps on demand and smaller if I have the time and inclination to smoke the sights black with a candle and the sun is behind me.
As to sighting it in, I found that it shot 2+" left and 2+" low when I first got it. I will not change my grip technique to cater to a particular gun but here's the story. With two hands the gps were about 2" left, but with one hand (the right one), they were almost 3" left. Correcting this without access to a good gunsmith to turn the barrel is difficult, and I didn't want to send it back to Ruger. In the end, I carefully widened the rear notch to the right with a set of jeweler's files, effectively "moving" the rear notch in that direction. That gave me an inch of the two I needed. I also filed about .015" off the right side of the front sight blade, as well as off the top. The top correction was necessary to raise my point of impact for my standard load: 255 gr SWC and 8.0 to 8.5 gr of new Unique. I took enough off to place that bullet 2" high at 25 yds. If I load 230 gr cast .45 ACP bullets, I find they hit about an inch low at 25 yds...still usable and somewhat lighter in recoil. The narrower front sight blade and widened rear notch have not affected the sight picture as far as I can determine. The piece groups as accurately now as it did before my efforts to correct the shot placement.
That pretty much did it and my gps are centered with a two-hand hold, and only an inch left when shooting with my right hand only. I used a cold blue to reblue the filed notch and blade and it's very difficult to see the changes.
As to ergonomics, I find the Vaquero with its rounded front sight and smooth notch rear is far easier to shove into my hip jeans pocket and the draw is much smoother. Too, in a Tom Threepersons type holster, it NEVER comes out with leather duff on the front sight. So, while the adjustable sights on the standard Blackhawks allow easy sighting in, they do have some disadvantages, primarily in carrying...
Don't get me wrong, the Lipsey's .44 Special is my favorite...but I do like the Vaquero a lot. Here's 3 pics of the work. If you look closely, you can see the widened rear notch, it doesn't take much on a 4-3/4 barrel to get the correction you need. I taped the hammer and adjacent frame to prevent the file from straying. It was file a little, then shoot a cpl of gps. Fortunately, I have a range off my back deck here on the farm so it was a morning's work to finish the job.
Regards and HTH's, Rodfac