Guided missiles being useless. I was totally crippled in my last game by Saladin. He started the war by using alot (alot, alot, alot) of missiles from subs, he destroyed my entire destroyer navy and most of my other ships that was at sea at the moment. Then he went home to reload, he got back a couple of turns later to bomb me some more. Oh, should I say that he bombed my oil resources with those "worthless" guided missiles, and he did that over and over again, until I got some destroyers out (from an ethanol company city, I had no uranium) and I could protect the waters around my oil resource.
For the most worthless unit, I must vote for the explorer (I sometimes use them for medics, but not often), except if you play on the terra map (the one with a undiscovered continent) where he can be good (with some proper promotions).