I actually found Legions loyalty quest a ridiculously easy decision to make at first. Okay so changing the Geths minds stops them being able to self-deteriminate in one scenario where they'd basically been brainwashed in the first place. Against that we have utterly destroying them which removes their ability to self-deteriminate in all scenarios.
You are a lot less free when you're involuntarily killed than in basically any other situation.
... wait a minute. I was going to end this bit with 'but then (I'm very much a Christian) I realised that God had basically made the other choice. He let us choose our own path to the extent that he would let us decide to die rather than change the part of us that turns away from him and good things...
But I just realised, no it's still really easily. God gave us the choice and went to enough effort to actually die so that we could have that choice and he works in the world everyday so that we know it's the choice we're making.
Whereas the Geth weren't given that choice. The right solution would have been 'Geth we're can either brainwash you or kill you, which do you want?' That is giving them the ability to self-deteriminate, as it is you're just choosing death for them.
I also agonised over the last choice in ME2 because I had to choose between what was obviously the right choice and the way to save the galaxy with myriad ways to prevent the only negative consequence happening. (Telling the Solarians about it and just getting the STG to frickin' kill any Cerberus dude trying to approach the Omega gate for instance) But I had to weigh that up against ME2 which was not going to let you do sensible things like that and treat it as though you weren't doing exactly what you'd done with the dead reaper before, and all the alien tech in ME1.
However the Krogan genophage. Still haven't worked that one out in my mind and I still can't decide. I chose to keep the data because, even if I decided against the cure I could just make sure that Solus didn't use the data.
But in all honesty, probably the hardest choice has been in the free flash game 'In The Company of Myself' where you choose between a death and not being able to progress with the game. Even now I wish I'd had the courage just to turn the game off and not press the button