Although not actually a defeat, but at the time it felt like it - The 2-2 draw (which was also the aggregate score) against QPR in the home semi final leg of the 1977 League Cup.
As I remember we went ahead, were pegged back (no away goals rule then in the LC at all of course). I seem to remember it went into extra time and we scored again to go ahead 2-1 - then they got a very late penalty which Burridge saved - only for (I think Eastoe) them to score shortly after - having victory snatched away felt like we'd lost. Of course at "neutral" Highbury shortly afterwards Brian Little firmly put them in their place.