I like my .22. I think the gun you can fire, and fire accurately, is the best. I have access to, and can shoot, almost anything, but still think I would flinch, in a serious need, with the .357, and some others. Loaded properly and being accurate with the .22 will ensure your wife hits the target, and walks away. I still prefer a revolver, as well. My .22 revolvers are easy to handle, and easy to be as accurate with, as pointing my finger. I like that comfort level, especially if we are talking about having it for protection.
Whatever you get your wife, make sure she gets LOTS of practice with it, so she is comfortable with it, and if she ever does have to pull it, she won't hesitate long enough to allow someone to take it away from her, and use it on her.