The wife & I just went thru this process over the last 6 months or so. A few tips.
Check out the Ladies Forum and read the thread BonnieB directed you towards. A LOT of very good info.
Involve her in the search. It is a personal thing for us guys. It is for the ladies too.
DO NOT rule out full size guns. Just because they're big, doesn't mean it won't fit them. My wife totally dug the double-stack FNX-9 (too bad we couldn't get our hands on one). The Ruger SR9 is also a double-stack 9mm with a very slender grip and good ergonomics for HER. She liked my 1911 with it's single stack grip, but the ergonomics just wasn't for her. The slide is too tough to rack and the slide lock and mag release are too far away.
SHOOT was she feels comfortable with. Like the others said-holding is different than shooting.
Consider your main use. Home defense? She has to be able to use/function under extreme stress, in the dark and place shots repeatedly accurately. That said, she needs to be able to TRAIN. That means a TON in ammo, training costs. Look at where ammo prices are today vs. 2-6 months ago. How much money are you willing to put downrange each weekend? Consider 250-400 rounds for practice initially. It goes fast.
If any conceal carry possibility, consider holster options too and even possibly different guns for different purposes. From what little I know of the subject, ladies have a much harder time concealing than men do.
I know it's a lot to consider. Your criteria is a bit different than my wife's. We are strictly the weekend target/plinker variety.
One thing that hasn't been brought up yet, how much training does your wife have? If she's inexperienced, maybe a cheap .22 would be good to start off with to get the fundamentals down? Is she already an accomplished shooter? Check out tactical training classes.
Anyways, do a LOT of homework. You've come to the right place! A LOT of very knowledgeable people here with TONS of experience. I am not one of them, but have learned a lot from everyone here. (THANKS CALGUN GUYS & GALS!).
Happy hunting and be safe!