When you say 'defensive,' surely you don't mean a carry gun, right?
Issues of bulk aside, I would rate the best red dot in the world as pretty much worthless. If you draw a handgun in self-defense, you're probably not going to be doing a lot of precise aiming. Point and shoot.
I'm sure some will say that's bullshit, or just plain irresponsible. Note that I'm not saying 'spray and pray.' I'm saying snap into your learned, practiced posture, and muscle memory should have you pretty on-target at a typical self-defense distance. The more time you have to aim, the more questionable your use of force is going to become. It's not the movies; you're not going to scream 'freeze, suckah!' You're going to shoot them as quickly as you can because you're in fear for your life.
That said, the only handgun I've fired with a red dot was a 10mm 1911, and it was useless. It was bigger than the sights that you're looking at, and the dot was hard to locate when you first brought the weapon up. The combo of a small sight and large distance between it and your eyes means it takes very little movement before it disappears off the edge of the glass. The time to acquire the dot versus the time it takes to acquire a good set of sights is going to be trivial, I think.
And of course, follow-up shots with a 10mm were nonexistant. Seems like anything more than a heavy 9mm (...like a polymer .45) and that dot is gonna say 'see ya!' after every shot. For me, it was really disorienting to try and reacquire it. The difference was that with normal sights, I never truly lose the front post. I know what direction I need to go to bring it back into my sight picture. Relying only on a red dot, I would nudge muzzle in the wrong damn direction trying to find the thing again.
edit: just checked, that was a Leupold Deltapoint that I tried.