This is interesting b/c one of my greatest successes indirectly lead to my biggest mistake:
On my first ever Civ (on Chieftain level), out of paranoia from getting harassed early, I built up a big military and ended up going from a huge science deficit early in the game to being THE power in everything by 2050 (and I won Histographically).
That was great, but I got SOOO used to NEVER, EVER giving in to anyone's demands for gifts or grossly unfair trades, that I was unwilling to give in even when I really needed to. In my second Civ (on Warlord), very early on, I snubbed the Egyptians when they asked for a gift, I didn't think twice about it. I've never seen so many War Chariots since!! They mowed 5 of my 6 cities down in a blink, and wouldn't recognize my envoy until I had one fledgling little city left. I gave them whatever gold I had and survivied. The problem was, I had only one city, and I was trapped on a peninsula, with no room to expand anywhere, and thus little, or really NO chance of ever getting bigger. I finished last out of 8 histographically, with a score of 143. Even to civs that got eliminated finished above me in score.
But it didn't all go down the toilet. The Egyptians eventually declined and by the 1930's when the Romans were about to finish them off, I walked in and got the last Egyptian city! Take that Cleopatra!