Obviously the first game deserves credit for its having saved Square from bankruptcy. In terms of raw sales, Final Fantasy VII was the most significant game. In terms of sheer progress over past installments, Final Fantasy VI takes the crown (and could have been the success that FF7 ended up being if only the game had gotten the kind of marketing and hype that FF7 did, as well as an actual worldwide release instead of a US/Japan-only release). In terms of modernizing the series, Final Fantasy X took the largest leap of any FF, even bigger than the jump to 2D/3D hybrid visuals seen in the PS1 FF games.
All of these are significant hallmarks in the series, and I don't personally feel that any of them are necessarily bigger than any of the others. Each, at the time of their release, was a game that gave the series an appreciated new direction.
Sky Render - Sanity is for the weak.
