My wife has ZERO interest in shooting.
Many years ago I figured this out and based the home defense on the lowest skill set in the house, which was her. I made things as simple as possible.
Point and shoot double action .38 Specials.
There are a couple stashed in the house, and when she carries, she carries a J Frame 442. Not the easiest gun to shoot, but I keep it loaded with wadcutters for her and it's very easy to operate. When she feels she wants more, its a 4" Combat Masterpiece.
On the HD side, if some dude is breaking in, I figure I can use whatever I grab and its not likely to make much difference outcome wise, if I pick up a Model 15 .38 Special revolver or a G19, but it might make a huge difference for her, so that is why I keep the double action .38s available for her.