The 64 and 65 are both great defense revolvers. Never count on anything to achieve the one shot stop myth.It happens,but it's foolish to count on it with any caliber of handgun. Placement and repeat hits are in your best interest.
It's personal preference,revolver or auto,but these days my wheel guns are mostly relegated to the backup role unless I'm feeling particularly frisky and invincable. I will,however,not turn down a good buy on a revo like the one you mentioned.
As someone else suggested,a lighter alloy frame .45 would probably solve your discomfort issues with carry,and there are many acceptable ones on the market that will give you a lifetime of good service with proper maintenance.