Friend, your best bet is to take your wife to a range and rent various handguns until she finds something that she is comfortable with.
That being said--if you are in a position to help make th3e choice, your post positively screams for a 1911 type pistol.
And don't be fooled--I have helped train female officers who have a real problem reaching a trigger on the XD pistols, HK's, SigSauers or even Glocks--but they used and handled a full sized Government Model very well.
If you want a shorter pistol, something along the lines of a Colt Defender would fit the bill. 1911 autos are available in .45 ACP (of course!), but are also readily available in .40 Smith and Wesson or 9mm as well.
Hiding in plain sight...