The choice between Hawke and the Grey Warden. Honestly, this was an incredibly easy choice for my first Inquisitor--I had Loghain as a Grey Warden and I've never been that attached to him.
But my next Inquisitor had the absolute worst choices of all possible options I could have had. I had my favourite Hawke, still in a relationship with Anders, and a romanced Warden Alistair who had just been talking about how much he loved my Warden and how they were going to be together forever and I just--
After I made my decision, I got back to Skyhold and had a letter from my Warden waiting for me, asking me to please look after Alistair because she didn't want him to die for the Inquisition. I still feel guilty about it. 
The worst part about this is that my younger sister is on her way to this quest right now with the exact same situation, but I can't warn her in advance because I promised not to spoil her. She keeps texting me about how cute Alistair is talking about her Warden and how she's so glad to see Hawke again and I'm just pretending to know nothing.