There are many posts (mainly by one individual) on how easy this game is to win. My post is how to make the game extremely difficult to win or at least in less than 200 turns.
First off pick a galaxy appropriate for the number of factions playing the game, this is what I suggest... ( I know I missed a few but, you get the idea)
With this many factions in the game it will difficult to colony rush your way to more than 10-20 planets. (even with abundant habitable planets/stars) I also suggest having all the minor races turned on as well.
Resources doesn't really matter (random is fine but, abundant just helps speed things along).
Pirates a must. the more the better will provide more of a challenge against any colony rushes.
Very slow game pace/technology rates and no tech trading. (This will prevent you from spamming the AI and trading techs, even fair trades.)
Now choose your difficulty. I recommend starting with godlike and working your way down as you loose. If anyone else has suggestions on how to make a game impossible to win, feel free to add suggestions