Quite simply, not enough rounds. A year or so ago there was this woman trapped in the attic with an intruder pursuing her. She emptied her wheel gun and the guy was still alive. Darren Wilson, a trained police officer, needed 10 rounds to stop his assailant. If he'd had a wheel gun, the gentle giant would have killed him. The FBI learned its lesson in the 1986 Miami shootout and got rid of its wheel guns.
Wheel guns are great if you're into cowboy shooting. But as a personal defense weapon, their only place might be as a backup gun. With my Glock 23 and two spare mags, I have 40 rounds at my disposal. And even if you have a couple of speed loaders, you only have 15 or 18 rounds max, and the average person can swap out mags much faster than the average person can eject empty casings and reload by hand or with speed loaders.
Bottom line, a semi automatic is a much better choice for personal defense, especially when faced with someone high on drugs, or multiple assailants.
Darren Wilson, a trained police officer, needed 10 rounds to stop his assailant....I’ve posted the whole story on FR so this is the short version. Us old cops were at the range and some rookies showed up with autos. The first round of firing had all the old wheelmen hitting 5-6 and 6-6 in the middle ring all killing shots. The rookies all fired sixteen shots each and the high kill ratio was three and usually one kill for the twelve rookies. I turned to my partner and said “Gonna be a lot of damage and innocent people killed in the near future.”