Not really on over penetration. If you use a suitable Jacketed hollow point you could shoot 38Special. Driving most expanding hollow points tend to make then expand much quicker and therefore penetrate less actually. The 357 is basically a 10mm ballistic twin and I have killed deer out to 125yrd with my 10mm carbine.

better home defense than a .357 revolver over penetration could be a problem but no more so than any good defense round adding 100-150 fps or more to a 357 revolver (which is what you get out of the rifle) just makes it more effective. there are many deer sized game animals killed every year with a .357

Most 357 bullets just don't do well beyond 50 yds, and then you still need a perfect shot. Self defense would be excellent. I'd stick with the .45 though.