I will repeat the names you will hear anywhere you ask a similar question as you have here; Glock, XD, S&W, SIG and Ruger. There are other great brands out there, but I believe these have the highest level of reliability.

For simplicity of tear down and cleaning, nothing beats a revolver. But, you are looking for an automatic. The closest thing to the simplicity of a revolver is a Glock. They are the AK 47s of the handguns yet have the accuracy of their competitors. Taking them apart and reassembling them blindfolded is something anyone can do after playing with one for 30 minutes.

Caliber ... I love 45 ACP. But that is just me and millions of other people who want their target to stop in their tracks. You being a large man, I wouldn't expect you to carry anything less. I am 5'10" and weigh 148lbs and have no issue firing heavy 230 grain bullets (a grain is a measurement of weight. There is four hundred and something in an ounce). Your wife may prefer a 9mm though.

I believe a person should use the most powerful weapon they can handle for not just the first shot, but the following shots. She may be able to handle a 45 shot, but how long will it take her to reacquire the target should she miss?

As you mentioned, go test some guns. Find a local gun dealer who rents guns and sling some lead down range. Just don't let the dealer talk you into buying their latest and greatest pistol that happens to be $800.

You can get two great weapons for less than $1000.