I'm going to parrot what most others have said, and suggest that you take your wife to look at handguns, and in the process try them out and find what she likes. If yous can rent/borrow some to try out, all the better.
First off, if you're looking for a gun that you can sometimes carry as an alternative to your current handgun, then get one for yourself. Your wife's gun needs to be suited to her first, and you second.
I can speak from experience when I say that it's not a matter that can be solved by asking a bunch of forum guys "what is best?" At the end of the day, it's about what your wife likes, not what you like, and definitely not what a bunch of random strangers on the internet like.
I have taught both my mother and girlfriend about guns over the past few years, and in the process taught them how to look for a gun that they like. Note that I didn't look for a gun for them, they tried things out and naturally gravitated to different options.
Now, it's important that you really let her look for what she likes. Of course there is major benefit to giving some advice along the way, such as letting her know that lighter guns have heavier felt recoil, or that perhaps neither .22lr nor .454 casull are particularly suited to self-defense, but in any case it's best to remain as free as bias as is possible. Just because I don't like slide-mounted safeties didn't mean I tried to turn my mom away from a Bersa Thunder .380, it just meant that it wasn't a gun that was suited for me.
On the topic of mechanical function, my belief is that the strong majority of Americans are more than intelligent enough to figure out how a semi-auto works. Most of us are trained to operate things that are orders of magnitude more complex than autoloaders, and can learn how a semi-auto works in a very short period of time. DA/SA is a complex action to try to describe, but everyone I explain it to gets it almost instantly once I demonstrate it using a visual aid (usually one of my handguns). The most important thing is that you aren't "dumbing down" the gun in order to fit a perceived deficiency in the ability to learn the action, and are instead making sure she gains an extreme amount of familiarity with the gun regardless of the action type (think of the phrase "like an extension of one's hand" when trying to figure out how well she should know the gun)
On the topic of physical factors, there are some physical considerations to be made, although they are almost always in a different place than people look. It is important to find a handgun that fits in terms of hand size/shape. Comfort while holding it is a large factor, as well as the way the handgun lines up with the rest of the arm. A good explanation of that
can be found here. Just because I am able to shoot my 4506 comfortably doesn't mean that it's the ideal gun for my girlfriend (it's too long in the grip for her), and just because you can shoot your G17 comfortably doesn't mean it's the ideal gun for your wife. (as an aside, I feel that the siderlock safety is far more dangerous as a safety mechanism than not having it at all, considering it forces you to violate one of the four basic rules of gun safety just to turn the safety on, but that is neither here nor there)
If your wife has the average build, a shotgun or rifle will not be too bulky for her. In fact, there are a great deal of long guns out there that are perfectly suited to people of smaller statures, and plenty that fit people of average weight/build. I myself weigh a measly 100lbs, and I can tell you in all confidence that a shotgun or intermediate caliber rifle is nowhere near too much to handle. However, the same aspects apply to long guns as handguns- it's all about finding what fits her and what she likes.
TL;DR- Let your wife choose what she likes. You may have good intentions trying to find the best gun for her by asking us, but the best way to do this is to have her be an active participant in the process.