This is definitely a subject whose time has come. I'm ramping up a couple of ideas for THE BEST DEFENSE 2014. I'm seriously looking at the Browning lever action (BLR) lightweight "Hog Stalker" take-down gun in .223 (my first choice) or .308.
Taylor's Alaskan break-down .44 Magnum Winchester 1892 clone with its 7+1 load of .44 Maggies. The Taylor's is a little longer but almost a pound lighter.
In either case I'd go with a revolver (hey, it's not a semi auto with one of those boxy springy things that so scare liberals) as the handgun...actually, ideally, 2 revolvers — a belt gun and a smaller gun that will function as a pocket pistol. If I go with the .223 BLR, I might look at a .357 revolver — once again, ammunition availability and versatility. On the Alaskan, I'd go for compatibility and opt for a .44 Magnum revolver. There are a couple of option, depending on your level of paranoia and your willingness to schlepp bags. If weight of the overall package is the number one consideration, I'd look at the Alaskan, a scandium-framed 329 S&W revolver and a Charter Bulldog as the pocket pistol. The .44 is a thumper, but without the range of the .223 (and, yes, there is the issue of 2 calibers, Special and Magnum). If weight was less of an issue, I'd go with the 4-inch Redhawk, which will probably be working years after the glaciers come south.
If I go with the .223 BLR, I'm going to suggest a .357 revolver. For weight, look at the lightweight S&Ws. For stone-like durability, the Ruger GP-100. I think the Ruger LCR is one of the best pocket pistols ever made, but there are plenty of other small frame S&Ws, Tauruses, Charters and what-have-you out there. In this case I'd go with a .357 version for ammo compatibility.
Just some work-in-process thoughts!