My overall favorite handgun caliber -- that is, if I could only pick one caliber to shoot for the rest of my life -- is the 9mm Parabellum.
Reasons?
It's effective for self-defense purposes.
It's the cheapest self-defense cartridge available, so sufficient practice and training is not as expensive as other self-defense rounds.
The recoil is light, and it is easily controllable.
It's widely available and easy to find.
Now, if I could only pick two calibers to shoot for the rest of my life, they would be the .22 LR and the .45 ACP.
Reasons?
The .22 LR is dirt cheap.
Recoil on the .22 LR is almost nonexistent, and it is great for introducing new shooters to firearms.
The .45 ACP is a very effective self-defense caliber.
The .45 ACP is not horribly expensive -- it costs more than 9mm of course, but it is not prohibitively expensive.
Even though the recoil of the .45 ACP is pretty hefty, it's not as "sharp" or "snappy" as calibers with higher velocities.
The .45 ACP, and especially the .22 LR, is widely available and easy to find.