First off, to answer the question "will you be hampered using a single shot". I've only had the opportunity to fire one shot from my Encore to date at a game animal. It was on the first day of last years muzzleloader season. One shot, one kill. I muzzleloader hunt quite a bit and I'm not used to a quick follow up shot. But, that's what a single shot does for you. It makes you slow down a bit and take your time. If you know in the back of your head you only have one shot you will make it count.
Although follow ups can become pretty fast with practice the whole point of a single shot, in my opinion, is elevating yourself to a higher level as a hunter. At first people look at you like you're crazy. But when they start to think about it a bit they then think that you may be a better hunter than the guys that sling lead at anything brown screaming through the woods. That is one of the main reasons I bought one - the challenge of getting by with just one shot, and making it count.
As far as caliber goes there are so many variables. If you're planning on short range shots where deer and bear will be the likely targets you may want to consider a heavy straight-walled cartridge like the .45-70. I have no experience with it but I doubt you need the distance of a .308 or 06. My personal favorite, because it is the one I grew up on, is the .308. In a single shot I'd go with the 06 though. You have a bit more versatility with it and a larger variety of factory loadings available. It would do well on either species and would give you the extra range should you ever need it.
Best of Luck to Ya.
Ranger413