I'll agree with the .500 S&W. Whether it can penetrate or not, the force of a 440 grain slug at 1600 fps will probably incapacitate someone, most likely killing them.
In .44 Magnum you can get 340 grains at 1400 fps from Buffalo Bore ammo, not too bad either. Those loads are Ruger only so get a Redhawk.
I believe either of those loads to the chest would do the job. Here is a Youtube video I found testing a .44 Magnum vs some expired body armor:
On the other hand I am not going to conceal carry a large bore revolver and tote it around. I was thinking about getting a laser for my Glock 19 to make head shots more of a realistic possibility, but I am not sure which laser to get.