I'll try to add my two cents. More information is needed before one can really answer and/or help you. You need to ask yourself (and answer) some of the following.
1.) Are YOU the only one shooting it.. or are there others involved, ie: wife/girlfriend, teenage/younger children, etc., etc.
2.) Is the firearm going to be kept/used in the home only.. or is it going to be packed too?
3.) Is there anything with your physical size/limitations that needs to be considered?
4.) You looking to do other things with the firearm, ie: target shooting, IPSC, steel plate, hunting, etc., etc.?
There are other things you need to consider, but.. having been around firearms for over 50 years, Vietnam Vet, law enforcement, managed a full service gun shop, etc., etc. let me throw out a few of my thoughts for you to consider.
The primary number one consideration in choosing a self-defense handgun is the following:
IT MUST FIT YOUR HAND CORRECTLY!
It can be the biggest, baddest caliber.. smallest, most compact.. largest capacity magazine.. most expensive.. have all the bells and whistles, etc., etc. and if it doesn't
FIT YOUR HAND CORRECTLY,
then your ability to accurately hit what your're aiming at is greatly diminished. If you have small hands and/or short stubby fingers, then getting a double stacked .45 ACP (as a example) just won't do it. All you have now is just a couple pounds of steel that you're better off throwing at someone.
Then again, if you have large hands and/or long fingers, then trying to use a sub-sub-compact might just be as (if not more) dangerous to you then it is to the one you're trying to point the firearm at.
With everything else being equal, (the handgun fits your hands and you have a choice of calibers, let's say .45 ACP or .40 S&W), it's always better to downsize one caliber if you find out you're not quite able to handle the larger size. You also need to take into consideration the ability of those in your family being able to handle the larger calibers also.
YOU might have all the experience in the world with both semi's and revolvers.. but you need to look at the "simplicity of operation" factor if a novice family member might be shooting it.
All of the above.. and then some, is needed to be thought about when one is considering the purchase and use of a self defense handgun.
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As a personal thought.. and I don't want you to think I'm contradicting myself with my comments I wrote above, but..
"ANY handgun is better than NO handgun when the crap hits the fan and things get down and dirty. That little 2 ounce piece of plastic and electronics called a 'cell phone' just ain't gonna get the job done!" 
Dakota Duce
"May All Your Flights Be Of Good Weather!" 
Besides, right now my only handgun is a .22 and I really really really want a new big bore! 
