For me it's impossible to pick between not just my favorite 16 bit FF's, but my favorite 2 FF's of all: IV and VI. For one: I grew up with these games, so they'll always hold sentimental/nostalgic value for me. Then there's the fact that both exemplify the two key components I look for in my FF's: a great story and a great soundtrack. BOTH of these games had great stories and sound tracks, so it certainly does make picking between them a bit tricky.
In the end, if there can be only one, I'll have to go with FFVI since it has by far my favorite (and if you ask me, the best over-all) villain in the franchise: Kefka. Why is he the best villain? Because he actually wins. He set out to become a mad god of magical power and guess what? He does it! He becomes a god. He destroys the world. He literally destroys villages and fries people just for his own amusement. For two whole years, the world is his playground and absolutely no one can stop him.
Now I haven't played every FF game out there, but to my knowledge Kefka is the only villain that actually wins. If this isn't true, I'm fine with being corrected. But I still like Kefka best because he's like if The Joker were an FF villain. =3