DYNAMICS. Synthed guitars lack it. But that being said, there are some songs that suit the synthed feel better than a real guitar would. Mostly because ALL of the elements are synthesized.
Lashmush also uses synth guitars, quite well, I might add.
I've gotten to the point now, where, when I'm listening to the song, I try not to listen to HOW it was created, but the song as a "whole". Cause I can still enjoy synthed guitars, if the song kicks ass. I have to open my mind to accept that it is just another branch of music, especially in this "synthesized" world.
It just has to be done well sound good, and not shitty, like the "OMG I JUST GOT FL AND LISTEN TO MY METAL" song.
With the dynamics of a person, nothing beats the sound of a guitarist using his feelings on a good solo, or aggressive rhythm. You can feel the anger, or the hate, or the love...