I have a new pair of headphones and they work with everything except Rune Classic. I get audio out of one earpiece instead of the usual two. Is this a known issue or could the game be incompatible with my PC's sound card? I tried searching for sound and came up with no answers.

I am having the same problem

Apparently Human Head Studios had a fix for the positional sound issues on their website at one point; and it was an uncommon issue but not rare. Sadly I cannot find that positional audio patch anywhere as links to it are now dead. Ah well, maybe someone has a back-up of it somewhere, which I hope to find soon as I am still looking.
Whatever the case, at least there's still rune gold, which is worth the price considering the physical copies of it go for a lot more than I'd like to spend.