Okay. Please open MP (window mode). Play the file and check your Windows sound mixer in taskbar. Can it be that MP is muted?
Yes! It's a separate setting that doesn't appear in the mixer normally, and I never noticed that! I must have pressed volume down inside MediaPortal at one point and it stayed that way (I normally only use the Windows volume and the receiver volume controls). That would also explain why I haven't heard button clicks in the GUI lately.
Thank you very much for the excellent diagnosis!
Which means presumably there should be no problem with mkv + FLAC/etc for all.