Ok, since I am in LE people have this debate all the time. I will give you my thought. Since you wife is not ever gun savy get her some thing that is Barney simple to shoot. So a Glock, Springfield or sililar weapon would be gun. Both have "safetys" that are not a switch style. Springfield has a safety on the trigger and on the back strap and Glock has a safety on the trigger as well. Also both compact or subcompact models can hold 8-10 rounds. Another good option would be the S&W AirWeight. It is a 5 round revolver and is avalible WITHOUT a hammer. This makes it very very easy use. Pull the trigger and the bullet comes out. So these are the guns I would look at: Glock 27, Springfield XD 3in Subcompact or the XD compact model is nice as well or the S&W AirWeight 380 revolver.
Another thing you should do is have her shoot various different sizes of guns. Although a small subcompact style gun seems like it would be the easiest for her to shoot because she is small and the gun is small that may not be the case. Smaller guns are actually HARDER to shoot because there is less of a grip to hold on to and since the barrel is shorter thus harder to aim. Just keep that in mind when looking. A longer barrel is going to keep the bullet going straighter for longer. But since you are looking into home defense so 5-10 feet you will just be point and shooting anyways. Your not having to knock a bowling pin down at 50 yards w a hand gun.
Lastly as far as caliber. How much knock down power do you want? Do you want her to have to pump the whole magazine in the guy before he stops or do you want her to fire a round or two put the guy to the ground and then have a few rounds left over just in case this dirtbag has a friend or two with him. The 9mm was the original weapon used in LE but, they learned soon that it did not have enough knock down power. So a lot of LE went to .45. This had great knock down power but, the velocity of a round that big was slow and the magazine compacity was small (7-9 rounds) So, they came up with the .40. This round has great knock down power and the magazines can hold in upwards of 17 rounds. I myself am a huge fan of the 40 caliber weapon. A 380 round is also a good round but, a bit violent and it causes some distruction.
These are just all my opinions and everybody has their own. Just giving some in site. Let us all know with what you go with.