I would say pick a combat sport that emphasizes the qualities you need to succeed in a real fight, timing, energy and motion. You need something where you are working with a resisting opponent, not in a rhythmic pattern, and not just standing there, but moving like you would in a real fight. That does not mean people have to get hurt or take each other's heads off, but doing a flow drill in kali or having an instructor shout commands while one person punches and other blocks does not develop any usable fighting skill. Something like boxing, kick boxing, muay thai works well for striking because you are hitting pads, hitting an opponent that is trying to move, and having someone try and hit you back. You discover quite quickly in that environment what works and what doesn't.
That doesnt mean that your wife has to get beat up her first day in class, or ever. A good school should take it to whatever level she wants. She might start doing some shadowboxing, learning footwork, eventually hitting the bag or pads. She might later on gear up and go light with a resisting, more experienced opponent. But she will know how to move, how to hit, and what to do is someone is hitting her. Alot of the traditional martial arts don't teach this way.
The same things goes for any grappling art. I see schools that supposedly teach some grappling, but when i watch the students roll they are not working against realistic resistance and are making alot of mistakes because of it. And again no one has to get hurt, though in grappling this is less of an issue because there is no striking.
At Straight Blast Gym they use the I method, which is Introduction, Isolation, and Integration. The instructor will teach a technique and then you practice it with an compliant partner (introduction). Then the instructor will bring the class back in and iron out any issues, and then you will drill with Isolation. There is where your partner is giving you enough reistance so you don't succeed all the time, but he is not shutting you down totally. This lets you build realistic timing and resistance. Say i am practicing a basic takedown, I'll shoot in, my partner might let me take him down a few times, then he will resist more so i have to work harder, at times not taking him down at all. Integration is grappling to submission but starting in the position you learned in class. So say we were working on the mount position, one person will start in mount and roll to submission, then when someone taps you switch and roll again. This lets them practicing what they just learned in a wide open roll, with all submissions and other positions being options as well.
Alot of people say that the ground is the last place to be in a fight, and i would agree. So i would say if you don't want to go to the ground, then learn what to do when people try to take you down, which means learning how to grapple. Then you will be able to stop their takedowns, or just take them down yourself and end up on top.
As far as weapons goes i think that self defense systems like Tony Blauer's stuff has alot of merit. Its easy to learn and based on gross body mechanics. its not pretty, but real fighting never is. I find for myself its much healthier to train BJJ/grappling for sport, know i have some realistic skills that may work if i ever have to use it, but realize if its multiple opponents or weapons that no fighting system will totally help me.
Matt Thorton explains all this much better in his blog.
Its work/family safe.
Sorry if the above is kind of a longish rant. Its always the first thing that comes to mind when i read about people wanting to choose a martial art. Its hard to know what to look for if you are new to it all.