Ruger has had (at least in the past) of having the Vaquero throats undersized, in spite of the diameter of the barrel. For example, the Old Model Vaqueros in .44-40 use(d) .429" groove diameter barrels, same as for their .44 Magnums. But the .44-40 cylinders were mostly .425"! It took awhile to get the chambers sized large and uniform enough to take .44-40 cartridges with .430" bullets, period. Should I have had the throats of my guns reamed out? Logic would say so. But I found that if I used hardcast (BHN 17-22) commercial bullets of .430" diameter, the slugs apparently squeeze down going through the throats, but due to the residual stresses in the bullet metal, they will re-expand in the forcing cone. I get excellent accuracy (1-5/8" groups) at 25 yds, on the bench, which is certainly good enough for CAS. I would NEVER think of shooting jacketed bullets through these tight throats, but, as I have interchangeable .44 Magnum cylinders for each of my CAS match guns, if I ever wanted to take them hunting, I would use the Maggie cylinders.
This is not to say that you should not CONSIDER having your .45 throats reamed out, but I can't be dogmatic about it.
As to the fixed sight Rugers shooting low, that is done intentionally so you can file the front blade down ONCE YOU HAVE DECIDED ON THE LOAD YOU WANT TO USE!