Most stupidly difficult mission (That shouldn't be): Slaying Ravana.
Mission that stumped me the longest: Destroying the Saturn in PI. It got much better once I learned about long-range Akhetons, though.
The Only
Mission Gaming Experience To Ever Induce Nausea And Cause Me A Headache: Second to last mission of Transcend.
between the weird currents pulling everything around funny, the rotating subspace skybox, and trying to hit and kill small, fast targets (took me something like 10 minutes on at least one of the wingmen!) I was very glad when it was over. Wouldn't have missed it for the world, though.
Most Memorable:
FS1 mission where you escort the transports carrying Ancients data... and the Lucifer shows up at the jump node you're headed for. Pants-crapping moment.
First time I played Apocalypse (the supernova is amazing when you don't know it's coming!
)
Every other mission in Blue Planet
Dragons in Asteroid Field Mission (a.k.a. ohcrapohcrapOHCRAPIMGONNADIE), Dream Mission, killing the Lucifer, second-to-last mission...
Derelict's
Dream mission, the one where the Nyarlathotep is brought out of subspace, the one where it awakes, and the one where you destroy it.
Fortune Hunters 2259: the one where you chase down a series of Centauri transports as they flee to their base, then try to make it out alive. A real bugger to finish, but a huge blast (and very memorable).
ST:R's He Who Rides The Tiger.