I've considered this same question when I chose my first firearm, what caliber should I get?
Most of us soon recognize that there's no real answer except one...get them all!
My inventory of handgun calibers are: .22lr, 9mm, .38 Special, .357 Magnum, .357 Sig, .40 S&W, and .45ACP.
Long Gun Calibers: .22lr, 5.56 or .223, 7mm Rem Mag, 12 gauge
Honestly, if I were to only choose one round, it would be up in the air between .40 S&W and .45ACP. .40 S&W being a better all around caliber while .45ACP is a perfect man stopper.