Didn't get to run it myself, but I used to coach at Ithaca College and I heard stories about their former course, which involved running up a ski slope. Twice.
And I vividly recall spectating at a NYSHS Federation meet at Sunken Meadow (where I also never got to run), wherein I saw a girl walking up the last steep hill and passing four others in the space of maybe 50 yards. These were State meet competitors!
If I have to be restricted to courses that I personally ran (I didn't run many), then I guess the old Cornell 5.1mi course may have been the toughest, though in the universe of xc courses it was of no more than average difficulty.
And in the Pacific I ran a rolling course that was made more difficult because twice you had to travel a stretch of road that was next to a tethered water buffalo. No danger from the water buffalo itself, but sometimes it would cross the road and stretch out its tether and you'd suddenly have to hurdle the rope (about three feet high).
Also, if you fell on that course (easy enough to do--pretty rugged footing over most of it), you'd typically land on the crushed coral that they used as the base for most of their roads. This would cut you up pretty well, and of course coral cuts typically last forever--I still have some scars, decades later.