Are there any cards you've played with, and had to remove from your deck, or fix by adding house rules? I've found that the one-activation-per-turn rule suggested by HPG solves a lot of problems (like Freedom Fighter Pinkie and Cheerilee). At first I was skeptical that it would be too restrictive, but then I remembered that "the specific overrides the general," so cards that say a card's power would activate (most notably Love Poisons) still work, which allows for some fun combos. Even still, I've found some cards to be too powerful or otherwise make the game less fun*.
Blazin’ Hot Wildfire (2014 Con Exclusive):
Some men just want to watch the world burn, and when one of them is in your playgroup, you can’t play with Wildfire. I’ve talked before about the importance of slicers**, but this card just makes it too easy to remove large portions of the grid. Pinkamena’s effect is at least limited to the ships touching the Pony card she caused to be discarded, but Wildfire can cause up to 3 Pony cards to be discarded, which could directly affect up to 10 ships, or affect ships in unrelated parts of the grid. Also, her power is single-purpose***, as opposed to Love Poisons, which can be used to activate Pony powers.
Breezies (2015 Con Exclusive):
There are a bunch of Goals that require playing a certain number of Ponies or making/breaking a certain number of ships, and this card makes them trivial to achieve, especially when you consider race/keyword/timeline-change ships. (I once playtested a card that counted as 3 Ponies, and it had the same problem. 2 Ponies seems to be the limit).
Cider Matron Apple Bloom (2014 Con Exclusive):
I once played a very long game where this card was used a lot. I suspect that activating this card’s power sapped the players of the resources they needed for the newly revealed Goals, but I need more data to confirm this. In the meantime, this card is sidelined.
*What constitutes a “fun” varies widely from player to player and group to group.
**cards that have powers which can cause Ship cards to be removed from the grid. The nickname comes from Aria’s power in the No-Holds-Barred expansion.
***Of course, slicers are pretty much the only way to get Ship cards into the discard pile so you can search for them