I think you should do what you feel at the time, what I do is say one point I am like "I am going to freakin kill that beatch" so I do it... I play my first play thought as a "Anything goes" so if I kill a main person and 'fail a quest' I leave it and carry on. And then the second play thought I plan who I go with and who I want to kill etc etc.
And no you don't lose your room but like Colonel Martyr said you can't turn in your Snow Globes for caps, so if you are going to kill him, turn the snow globes in with, Jane (the robot who deals with them) and then kill him.