If deep penetration and expansion is what you want, that's fairly easy to get if you know what cartridges to look at. Most magnum-class cartridges from .41 Magnum and up can give you both expansion and 16+" of penetration so long as too light and/or fragile a bullet isn't used. A bonded or "controlled expansion" JHP like Speer Gold Dot, Winchester Platinum Tip, or Hornady XTP should be more that capable of giving you the desired result in .41 Magnum or bigger.
Like others, however, I rather doubt the usefulness of such a deep penetrating loading outside of hunting. There are a few problems with a defensive loading which penetrates in excess of 16-18". The first issue is that the risk of overpenetration is increased. You see, even the FBI minimum of 12" is enough to be a through and through shot if we assume a small-to average sized adult male, a straight-on frontal shot to the upper torso, and no intermediate barriers. Because we don't really need, or even necessarily want through and through penetration, the 12+" standard is really more than what is necessary for many, if not most, situations. The reason that 12" was arrived at as the minimum is to compensate for an extremely large individual, a shot at an oblique angle, and/or intermediate barriers. The thought is that even though we really don't want through and through penetration, it's still better than underpenetration.
That being said, a cartridge which falls within the 12-16" penetration range will shed a great deal of velocity going through someone. Even if it does pass completely through, its velocity coming out the other side will most likely be reduced to the point that the risk to bystanders, while not completely eliminated, will be greatly reduced. A bullet which penetrates 18+", on the other hand, almost guarantees through and through penetration of unarmored targets and will very likely plow on through with enough retained velocity to still pose a significant risk to bystanders.
The other problem is that handgun bullets which penetrate this deeply often display very moderate expansion and/or expand much less rapidly. A JHP handgun bullet which routinely penetrates 18+" in ballistic gel will likely not expand at all or expand very little in an average erect biped. What we really want in a defensive handgun bullet is one that expands as rapidly and violently as possible without sacrificing adequate (12+") penetration. A bullet which is only beginning to expand as it leaves the target is only slightly better than one which does not expand at all. If all you want is through and through penetration without regard to expansion, just about any caliber from .32 Auto up can pretty much guarantee it with FMJ or other non-expanding bullets.
Finally, a perhaps most significantly, the cartridges which are most capable of providing the performance you describe are usually very large, powerful cartridges that come in big, heavy guns and generate a lot of flash, blast, and recoil. While there are certainly people who can do it, someone who can shoot a full-power .41 or .44 Magnum, much less something bigger, both quickly and accurately is somewhat rare. I am a fairly large person (6'4" and 285 lbs) and an all-steel, large frame .44 Magnum is the very upper limit of what I can shoot with what I consider adequate speed and accuracy, and even then only with mild-to-moderate power loadings and carefully selected grips which fit my hands well. For the majority of people, a full-power .357 Magnum or 10mm Auto from a medium-to-large frame all steel handgun is probably the upper limit, and a more moderate "service" cartridge like .38 Special, 9mm, .357 Sig, .40 S&W, .44 Special, or .45 ACP will generally be an even better choice. Quite simply, a big, powerful gun isn't useful if it's too much for the shooter to handle.
