You said the purpose is defense, it that for concealed carry on a regular basis or more for home-defense?
The 125gr .357mag round is far above any other cartridge for it's record of "one shot stops". There is also nothing more simple, fail-proof, and relaible than a revolver. For concealed carry duty I use a SP101, it carries five shots of full-power .357s in about the smalles form-factor available. The problem with a .357 revolver that is small enough for easy concealment in all weather is that it will not be suitable as a pleasure weapon, that little sucker kicks like a mule. I use .38+P for practise to mitigate that "feature".
The same is true for the .45ACP but to a lesser extent. Even the smallest .45ACP semi-auto is somewhat problematic for concealment and comfort, particularly for summer and folks who do not have a large body mass. If you really want to carry a semi-auto pistol then the .40SW is a good alternative to the 9mm. It sorta fills in right between the .45 and the nine as far as delivering foot-pounds to your threat. But for a nice small package that can hide under a T-shirt the 9mm is hard to beat, and it certainly carries enough power to keep you alive if you shoot well. If you cannot shoot well enough to guarantee that then even the .454-Casull wont cut it.
If concealment is not an issue and you are looking for home defense your shotgun is hard to beat but there's a vociferous crowd who like the CAR-15 or M4gery for such duty. With the use of frangible bullets they have been demonstrated to be less penetrative than 00-buck.
ETA: Goob, you are right in your assesment of the power delivery capacity of the .44mag versus the .357mag, but studies show that for thin skinned game it is actually OVER penetrative, simple truth is most of the energy gets delivered downrange of the target rather than into it. In fact the same is true for the .45ACP since the .38SW has a better one shot stop record than the .45ACP, there seems to be something about the 125gr .357 that causes an explosive effect to the bullet while the big 230gr bullets just blow right on through.