To answer the OP's question I would say a .30-06 in a good bolt gun topped with a Leupold 3-9 or 4-12 scope, and shooting whichever 168 or 180 grain hunting bullets that grouped best in that rifle.
At this stage of my life, I have a pretty good battery of rifles in my safe, but if I had to choose just one for any of North America's big game, except maybe coastal brownies or polar bears, or if its raining, I would grab my .300 Weatherby. Its topped with a Leupold VX-3 4.5-14x40 CDS scope, and would shoot either my Barnes 168 or 180 grain TTSX handloads.
For rainy weather, I'd pick my Rem 700 Stainless/synthetic in 7 mm Rem mag, that is topped with a Nikon Prostaff 4-12x40 with the BDC reticle, and shoot my 160 grain Nosler accubond handloads.