So here's my relatively low-end setup:

From the computer I have fw400 going out to Behringer's FCA202 external sound card. From the sound card I have two 1/4" trs cables to the Behringer Xenyx 802 mixer (I also have two cables going from the mixer back into the sound card, so it can accept input from the mixer). I have been using headphones hooked into the mixer for some time now, but I just picked up a pair of used BX5s.

The BX5s sound great when I fire up iTunes, so I know my problem is not with these new speakers. However, I've been working on a short film for fun and, anytime I play back what's in my timeline the audio pops non-stop. I also have some .mov files saved on data dvds and when I play them back I also get popping. I do not get popping when playing back commercial dvds. The computer has a dual-core processor and 8gb of RAM.

This seems to be an issue with latency somewhere in the chain, but I don't know where or how to fix it and it's driving me NUTS. Anyone have a solution?

You could check the sound card latency/buffer settings.. also your bit rates, sometimes if you run a 48k/24 bit signal in but the computer's expecting 44.1/16 it can cause pops (or your editing program might be set up for a different bit rate than the file you're working with). could also pop when you're running your signal too loud, etc..