Just like any other tool, Big works better in some cases and small works better in some. Match the tool to the job and you will do fine. As we all know, the 30-06 has killed every species of game on earth and is a good place to start. Keep in mind that legal issues might determine what you use in some places. For all of North America something like the 270/30/06 and a 375 H&H/Ruger would cover the big game end very well. For one gun, maybe the 300 WM.