30-06. The answer is always 30-06.
The .30/06 is an answer as is every other cartridge mentioned thus far, but confidence is the illusive quality we search for in our rifles. Our personal experience, or lack there of, may rightly or wrongly support the confidence we have in our rifles and loads. With the choice of an appropriate bullet, any modern cartridge of 6.5 or larger is certainly capable of taking any North American game, and much African and Asian game as well. But choose an inappropriate bullet and your confidence in the rifle, the cartridge and the load is lost unless the failure can be examined in a dispassionate fashion.
I have had a number of bullet failures with the .30/06 cartridge, but no one will suggest that the .30/06 is not a good big game round. Upon examination I was able to say, "Yup I screwed up and chose the wrong bullet!" Note I did not say that it was a bum bullet, only that I chose the wrong one for the job at hand. As a result I have the experience to be confident that my .30/06 is able to handle any situation I choose it for, whether the target is a moose, a big bear, a caribou, or a piece of paper a half mile distant.
I also have confidence in my .375. It is the consummate custom rifle. Not that is it showy, but just picking it up exudes confidence, and its performance only enhances that confidence. It is short, and business-like, and shrugs off the riggers of inclement weather. It cycles everything I feed it without a hiccup. When brought to shoulder the sights are right where they need to be, I don't have to move around on the stock to attain a proper sight picture. If this rifle was half as accurate as it is, it would still be twice as accurate as it needed to be. It takes small species of game without undue damage, yet kills medium and large species with authority out as far as I am willing to shoot at live targets. Recoil is exhilarating without being debilitating. With such a rifle I need no other. Now that's confidence.
Just as importantly, because I have experienced bullet failures on live targets, so I am less inclined to stray from what I know works. I don't fully embrace the whole light bullet at high velocity concept for big game, yet I recognize that bullet technology has come leaps and bounds from when I picked up my first rifle. Some have suggested that as a result I am living in the past, but I do so with confidence, and how can you be confident of a new technology that works outside the parameters of accepted performance? By the time you've used the new technology enough to gain or loose confidence in it, it will have been eclipsed by something else. Having said that, I was suspicious of the TSX when it came out. But over time I have developed a grudging appreciation for this backwards designed bullet, but I still prefer not to have a big game bullet impact at 3000 fps, that's varmint rifle territory.