My favorite LOFT was in the DC-8 sim when I was a Co-Pilot. Just after rotation and lift-off the Captain had a "heart attack" or something and slumped forward. I told the Engineer to grab him and hold him back away from the control column. I requested immediate return to the field but naturally it was "socked in" - Zero-Zero and I had to find another place to go. We had taken off from LAX. "ATC" told me the only airport with minimums was SFO, so I told them I was headed that way. They gave me some long-winded clearance to which I answered, "No way, I'm headed DIRECT to the SFO 28L Outer Marker and I'll be flying at 26000 feet." They accepted and away I went. Rest of flight uneventful. Oh, I called the Stew and asked her to find out if there was a Doctor on board and all that stuff. Landed SFO and that part of the LOFT was over. I passed !
There's almost unlimited scenerios one can come up with. It makes for very good training I think.