Did you enjoy the game more on your second or third run?

I do enjoy my subsequent playthroughs a lot. Nothing can beat the initial wonder and excitement of a first playthrough, so I wouldn't say that I definitely enjoy later playthroughs more, but being able to control the pacing (in leaving out stuff that isn't critical for the main path or that one simply didn't like the first time) really lets me enjoy the game multiple times. Also being able to play a totally different character from an ability standpoint (played a mix between biotic, vanguard and engineer the first three playthroughs, while focusing solely on an engineer/infiltrator mix in my fourth) is a lot of fun IMO.

After going mainly with singularity, charge and energy drain the first few runs, I had a blast going with tactical cloak, incinerate and energy drain in my last run. I always focus on maxing out powers and passives, so I still have a lot of combinations left that I could try in further playthroughs.