I have played several games at the highest difficulty allowed and I am wiping out the AI every time. 

But seriously...

In my last game, Mars colony had a zero population throughout the game. I am 99.9 percent certain that the original colony ship had a full compliment and future efforts to send in more population were not successful. May never happen again, but it happened this time, and could not be corrected in-game.

Planetary population is not correct on the right hand side panel, (planets, ships, starbases)

Tooltip dialogues interfere and overlap each other on the map and at the bottom of the screen. 

There should be a better way to alert for new ships. I have had colony ships piling up unejected because I was not advised they were completed. This is the biggest problem I have had, so far. I have read that the ship production routine will be totally revamped so maybe this is not a big deal right now.

Another annoying quirk is the planet production screen. There are six categories of improvements, Manufacturing, Research, Wealth, Tourism, Population and Influence. There are no categories named Economic or Production improvements, but the hex bonuses refer to these categories. Is a factory an economical improvement, or a production improvement? Arguably it is both. Is a Market Center economic, wealth and production? It might be considered all three. This is a potentially confusing issue that can be avoided simply by sticking to the six named categories when referring to bonuses.