9mm is the cheapest defense round you can buy, with FMJ cartridges widely available for under $.10 apiece. The Glock 17 or its slightly smaller, more concealable sibling, the model 19, are the best way to carry and shoot this round.
The Glock semi-auto design is so simple, so widely recognized, and so thoroughly proven, that this pistol wins based not only on simplicity but also on ubiquity and durability. The polymer frame keeps it very light. The slide is also the only semi-auto with a factory spring light enough for my wife to reliably cycle. Cleaning, if necessary at all, is a cinch: You remove the slide, pop out the recoil spring, remove the barrel, scrub and lube them all, and then put it back together. Show above is a first generation Glock 17 from the mid 1980’s. I don’t know how many thousands of rounds have gone through it, but that’s the extent of its cleaning, and I can’t remember ever having a non-operator-induced malfunction.
You can buy a new Glock for under $500. Put tritium sights on it for another $100. Get a holster, load up its 17-round magazines with cheap ammunition, and get to a range to hone your skills. For defensive use, especially if you don’t have a military or police background, you owe it to yourself to get some professional training. Local NRA-affiliated organizations or shooting clubs should be able to steer you in the right direction. (I qualified expert on the M9 in the Air Force, and subsequently spent 3 productive days at the SigArms Academy’s Concealed Carry course for civilians.)
There are a plethora of semi-automatic pistols on the market. Right off the bat I rule out any with an external safety: A well-designed handgun is drop-safe, so it doesn’t need a manual safety. The gun’s operator keeps the gun safe by keeping it holstered, and when it is unholstered the operator keeps it safe by not pulling the trigger unless he wants to discharge a round. I also rule out guns with exposed hammers or double actions: These are unnecessary complications that may be fine for competitive shooters, but which should not be brought into the equation for civilians just trying to acquire or maintain basic competency.
The only drawback to the Glock series is that it uses “double-stack” magazines, which means the grips are larger and not suited to people with small hands. If you have small hands, find a single-stack gun that fits you — that’s more important than any other feature.
Finally, if you don’t already have a safe, buy one of these and bolt it into a cupboard or closet. (You can find them on Gunbroker.com for under $100.)
Update: this is a photo of a third generation Glock 17. Its frame has more aggressive grip moldings as well as a front rail for attaching lights and laser sights — in this case a Streamlight TLR-2 unit that combines both.