Wanted to chime in as I've been having this problem for several months now.
I have a MBP Retina 15" 2013 connected to a 24" Apple LED Cinema Display. Typically my sound runs through the Display, tho occasionally will use phones for sound work in Final Cut or ProTools (tho the latter runs through my MBox). Prior to the Yosemite update, I had no sound issues whatsoever, whether running from the laptop, through the display, or using multiple programs handling sound and media.
After the update, intermittently, my sound will crackle and/or to cut out depending on the program that the source is coming from. This usually occurs when I have World of Warcraft, Safari, and Mumble up and running at the same time. Each program responds to this issue differently. Generally when I notice this issue, it's because voices through Mumble become crackly, and the sound in WoW starts to warble (cut in and out rapidly that it sounds like an echo, but it's not repeating sounds). Media played in Safari will have no sound. And when adjusting volume from the keyboard, the indicator tones either are extremely delayed or do not play at all. When speaking in Mumble, no one can hear me, or my voice is distorted. Usually to regain sound, I have to quit out of all three of these programs, then restart them all. Rarely do I have to restart my whole system, but I've done that on occasion to see if I can prolong it's reoccurence. Less often, I will hear people fine through Mumble, but my voice isn't working, or is extremely distorted and I must restart Mumble and WoW. I thought it was a Mumble issue, but the issue occasionally will occur when I just have Safari and WoW open--the sound in WoW starts to warble and sounds in video in Safari won't play at all.
Unfortunately the problem is intermittent--sometimes it will not occur for a whole day or session, but other times it may happen several times back to back. Even after a full restart. But it does seem to occur more when Safari hasn't been shut down for a long time. Lately I've been trying to run WoW, Safari, and Mumble with no other programs to see if that prevents the issue, but no surefire success yet.
What's most frustrating is prior to this update, my Mac was seemingly bombproof and I could run all three plus several Adobe programs, Pro Tools, Final Cut X, etc, etc without a bobble in the system.
This thread is interesting and I'm going through the solutions one by one. I haven't checked to see if it may be an output issue, so will see if just switching sound to the laptop or headphones may clear up the issue.