Tried with a Zagg, and it didn't work out too well. You have to really press to the point it's no more natural/intuitive. Also, I got the Defender for about 3 weeks now, and the front screen protector has kinda became a little more "looser" from regular use. Like now when I have to press a button in any extreme side of the screen, I have to push harder. So I guess if you keep a screen protector on, I think you might get frustrated big time and might want to throw your iphone through the window.
As far as I love my Defender, it's far from the perfect case for everyday use. It basically won't fit any mount or cradle, is bulky in my jeans pocket and it's pretty heavy for a case. Still, I think it gives me a better grip over my ip4, and I have kind of a curse which makes me break everything I love unintentionally.
So it is really practical, and I can assure you, it really IS the best protection you can get for your iphone.
Since you seem to have the same problem as me (if you were to leave your iphone in the defender all the time you wouldn't ask this, I guess), here's what I'm about to do: buy 50 cheap protective covers on ebay for 12$. So everytime I will put my ip4 out of my defender for another case, I will put a new protector on.
Sad but it's the best solution I found.