Not much margin for error with a six gun because none of them shoot very flat beyond 60-70 yds. For hunting, especially with iron sights you have to be very careful about how far you are willing to pull the trigger.
Shooting a six gun at long range is great fun & I do it all the time but it's mostly rocks, stumps, varmints, Utah fisherman, etc.
I always paint my sights (old eyes) white with a felt marker, etc. let it dry & then bright orange, or red but I only paint it about 1/3 down the sight, the bottom of that paint I use as a long range reference. I shoot & see where that line zero's at & that gives me a second sighting zero. Makes it pretty handy for shooting out to 200-300 yds depending on how far down you've painted.
Forgot, I normally zero about 2" high at 50 yds, usually puts me close to dead on at 100 yds & around 7-9 inches down at 150 yds with iron sights depending on caliber & velocity. Probably my favorite is the 10.5" 357 Maximum with a 185 gr cast HP.