I'm all about muddying the water a bit!
I'm pretty set on the 223/308 combo. Not only do I have a good feel for the ballistics of both calibers, but I have a healthy stockpile of ammo set up for both calibers, as well as components, reloading equipment and dies for both. Between 308 and 762x39 I'm covered for intermediate and long range target shooting, as well as taking most game on this continent. If I were to go for bigger/better ballistics as well as ELR stuff I think I'm pretty sold on going with 300WSM, 300PRC, and/or 300WM. Keeping things in the 30cal range would help me keep things economical.
I have been pretty interested in 6.8 western and similar .277 cartridges, but have no immediate plans to purchase.