I do not do a lot of handgun hunting for medium/large game, and I am certainly no expert on the matter, but I have taken a few of whitetails with them. For me the variables power scopes are difficult to use for medium sized game at ranges of 100 yards or less and I vastly prefer a fixed power 2X or 2.5X EER. The only time I find the higher power scopes useful is when I have a .223 barrel on a T/C for groundhogs, etc. in an open field.
Both Ruger and S&W are fine choices for a wheelgun.