Hello there!
I've just jumper on the PlayOnLinux wagon a little bit ago, and so far I'm really impressed! Of course you have some problems here and there but for the most part it's really "plug and play" :).
Now, onto my problem. I've got two computers (laptop and stationary) with the same setup. Both are running Xubuntu 12.04 with Compiz (which I switch back to Xfwm4 when playing games so they run better). Both also have the "latest" (at least the latest you can get through additional drivers dialog) Nvidia drivers. The only difference I can think of is that on my laptop I kept gmusicbrowser, and on my PC I already switched to Rhytmbox (and deleted gmusicbrowser). Since I didn't touch any sound settings, they should be the same.
And yet, on my laptop, sound works just fine in LoL, while on my PC, sound stops as soon as I enter a game (doesn't matter if it's spectator or normal). Also, it usually doesn't come back if I leave the game. I've already tried reinstalling LoL but that didn't seem to do the trick (even though, they say the third times the charm :P). After messing around a bit I've started getting some errors on LoL startup too here and there (invalid arguments) so it might be better to just do a clean re-install.
Extra info:
When I start the game on my laptop, I can immediately see an "ALSA plug-in [wine-preloader]: ALSA Playback" under Pulseaudio volume control -> playback.
On my PC however, the volume stream is never there - even when sound plays in the login menu there is no stream.
Any ideas? :)
PS: Another difference would be that laptop uses it's own speakers, but on my PC I use 5.1 audio.