Hmmm, do you mean S1 E6, The Trail? When Liv had them sit in that hotel room and hash it out and Fitz mentioned something about a "dead marriage"?
I think Mellie would have lots to gain and right now she is hypersensitive (compound that w/ Fitz still dreaming of Olivia in his sleep!!!), so a ruthless decision like that is not too far field. If Fitz were to be assassinated, she could build her own political platform on how she survived being the grieving pregnant First Lady of a great POTUS who accomplished a great deal during such a short tenure in office (Dream Act, successful non-military intervention, etc...). Having a celebrated former president as a spouse is much better than having one run out of office because of adultery or election rigging.
All in all, I hope it is not her. I want to believe that she is good deeeeeeeep down inside. I mean, she did mention building Fitz up from the emotional wreck that his father left him...