Pick the one that fits you best and that you and any other member of your family that's qualified, can shoot well. Either round, with today's boutique self-defense ammunition, will do the trick if you can provide the necessary shot placement.
I like the bigger calibers: .40, .41, .44 & .45. But my wife just doesn't handle them well so her choice is a S&W .38 Special on her night stand and usually in her purse. My wife and DIL have both been in situations where their access to a hand gun would have saved the day. Neither had to resort to its use, but were VERY glad it was there, ready if needed.
Unlike bicycle riding, shooting effectively in an SD situation is very perishable skill. You owe it to your family to get out and practice and bring your wife along. Make it fun and she'll shoot too. Conversely, if the gun/caliber/recoil etc. is not to her liking, you'll have a devil of a time getting her the necessary range time.
Best Regards, Rod.