Sanderxpander
A lot of it is in the playing technique. If you play the way a guitarist might actually play the part, a relatively mediocre sample through a decent ampsim can suffice, whereas even the best sampled guitar will sound like a keyboard if you simple hammer the line in like you might on a keyboard.
It's worth spending some time learning guitar specific phrasings and articulations. Some plugins do help with this by offering short lines or automatic hammer-ons or bends and so on.
+1 from me.
Learn how a guitarist plays, and put it through a guitar amp/amp sim.
Jan Hammer did some incredible playing using A Moog or a Fender Rhodes. Listen to his album "Black Sheep" from the late seventies. It is as much how /what you play as anything else.
Someone (I think it was the "Times" newspaper) once asked Jeff Beck who his favourite guitar player was, and he answered "Jan Hammer".