Have carried both rounds as primary duty caliber, and will stay with the 45 ACP.
Whenever the debate is started, and it is a wonderful topic that will never be decided, I try to recommend to those new to defensive shooting the following:
1. Chose the largest caliber/handgun platform that you can accurately control. It is a true statement that a hit with a 22 is far better than a miss with a 44 Mag. - Cannot give adequate credit to the person I heard this from.
Two points here - a big hole is better than a little hole (this one is mine) but shot placement is King, adequate penetration is Queen, all else is angels dancing on the head of pin (I'm quoting my friend Erich on this board for this priceless wisdom).
2. Then practice, practice and practice as much as you can in the situations you find yourself in. They need to be real life situations, example drawing from inside the car, situations inside your house, night time, do a little exercise, get your heart rate up, have to breathe a little faster and deeper when shooting. Shoot with your weak hand.
You can certainly practice marksmanship, trigger control and such at the range but how many shoot outs (I hope you never have to find out) will be done under "sterile" conditions you find at the range.
3. Learn to avoid the situations that might put you in the position to be in a shooting.
Make keen awareness your very best friend, know your surroundings, know your escape routes, how can you get the hell out of there so you need not be in that situation.
I know I have drifted a bit from your original question and I hope you find this helpful.
Pawncop... I can't pass up saying that was some of the best advice and sage wisdom I've seen posted on a forum. It is all too easy to get embroiled in the subject of what gun/caliber one should buy and not consider or even know to consider the salient points you've mentioned, when making the choice.
"Practice using real life situations", absolutely! It really is different when the adrenalin is pumping, the shooting conditions and/or position not optimal, and the length of time that you're dealt with to do all of things needed to make an effective shot, that makes it important to practice in the areas of the home, in light and darkness, where you are most likely to find yourself needing to employ deadly force.
Those are factors that you may have little or no control over, and range practice alone can lull a person into a false sense of security because when they're at the range, they can consistiently put their shots in the black in a relatively controlled setting.
But the BEST bit of advice given was "Learn to avoid the situations that might put you in the position to be in a shooting".
I have some personal experience there, and without going into the sorted details, the aftermath taught me just how dumb of a decision it was for me to confront rather than exercise the smarter and safer option of evasion, and I'm lucky to be here writing this.
So hat's off to you.
Now to give my .02 worth on the OP's question, I've actually settled on two guns for self protection, one when I doing a lot of car travel, and the other for the rest of the time.
The "car gun" is a revolver for it's ease of operation (no safety to operate), ability to readily use it strong or weak hand, no flying brass in a confined space to potentially distract. It's carried cross draw for an easier draw while sitting, and it's
a .44 Spl.
The house gun is a 3rd gen 4516, the variety of factory ammo available in the .45acp to suit the need (defense or target) is 2nd to none, and I've found that it's compactness is easier to handle in awkward shooting positions.
I do like the 4006 for it's various merits and it's one of my favorite range guns, but I can't shoot it effectively as a SD weapon as the 4516, and to me that makes the extra rounds in the 4006 less meaningful.
