It was more the English than the Appalachians. Sure, they could cause some trouble, but the English actively stationing troops across the forts there were the primary reason the colonies didn't spread into the area so early.
Well, more the natives (who tended to get upset about settlers setting up shop on their hunting lands), the isolation (starvation was a real problem when you have few neighbors to rely on, especially since it was the tail-end of the Little Ice Age), the land quality (the Appalachians themselves are basically hills, which limits how much farming you can do; there's a reason plantation agriculture never took off in Appalachia, unlike much of the rest of the South on either side of the mountains, and past it you had fairly dense forests that had to be cleared), and transportation (the mountains mean you have to deal with waterfalls, which make it a pain to ship things by water, and shipping by land is always going to be slower and more expensive before the invention of the railroad). All that can be reflected by the land being poorer, not impassible.
Armies did cross the mountains, after all: Braddock's expedition and later expeditions against Fort Duquesne, along with the various other conflicts in the Ohio Valley all involved armies from the East Coast crossing the mountains to launch an offensive (and note that, getting back to the dense forests aspect, the route that Braddock cleared later became a major federal road, and later an interstate highway). By the time of the Civil War, you see multiple campaigns fought in the Appalachians (for example, the Western Virginia Campaign, which saw an army from Ohio fight an army from Virginia over control of what would become West Virginia).
The Rockies (much taller and more dangerous) clearly were a barrier, but they are mostly wasteland already.
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