Hmm...
For Wild World, using Action Replay and SAVING it onto my town (I don't even know what I was thinking... T-T) caused me to be annoyed by it later on and to reset my first ever town in the Animal Crossing series. That was my biggest mistake.
In both Wild World and City Folk, I regret time travelling. Once I realized it wasn't any fun anymore, I went back to playing day-by-day and enjoyed that much more. I have never time traveled on my New Leaf town, and never will.
On New Leaf, I haven't done anything too regrettable, thankfully.
I can't really think of any other major mistakes I've made, so I think I've had an overall good experience with the series.