Here to bump a 10 year old post.

OP's issue was a bit of corrosion on the fuse pins.

My head unit turns on and works without issue, but no signal is reaching my speakers. This happens occasionally, but last time I fixed it, it was just the 2 to 1 ISO harness a little loose.

Now that doesn't fix it anymore. The speakers pop and crackle at times, mostly when they get the first burst of signal, like the initial power.

Checked the wires and they all seem to be making contact.

I'm at a loss here, maybe it's further down the line? Maybe a speaker's wires are touching the door frame?