This is the old Jack O'Connor vs Elmer Keith discussion. Been going on for a while...His theory was that "velocity" vs ft lb's of energy was a swifter and more humane method of dispatching large game. That the hydaulic effect created by the velocity was far more devasting than a heavier/ slower bullet...
I think, as you say, shot placement is what it's really all about.
I would not want to try to shoot an unhappy tiger with a handgun, but, if I had to, a 44 mag would be a good choice...