Obviously, first and foremost would be Stan Lee & Jack Kirby's 100-issue run. That stuff was gold from the beginning.
I've never read it, but John Byrne's run is supposed to be quite good. You can find them in trade for under the Visionaires line.
The run that got me personally into Fantastic Four was Mark Waid and Mike Wieringo's run, starting with FF #60 (Vol.3). Eventually, they went back to the series' original numbering, so their run ends around #524. I believe there's a new series of trades coming out for that run.
Don't bother with Mark Millar's dreck run.
Again, haven't read it, but apparently Jonathan Hickman's current run on Fantastic Four is quite good. It technically starts with the Dark Reign mini-series, and then officially starts at #570.