My first experience with this story was Heston's "The Omega Man", which at the time was great. But I feel this one beats it by a mile, primarily because Will Smith is much more believable as Dr. Neville than Charlton Heston was. In particular, Heston's Neville came across as too omnipotent and omniscient, whereas Smith's Neville is a real-live vulnerable and insecure human.
I agree with at least one other reviewer that this really should have had a running commentary available, ideally from Will Smith. It also begs for a "making of" extra feature.
One other sorta-negative comment relates to the alternate ending, which I haven't seen yet but I'm currently watching the disk 2 version which includes that. I'm not aware of any changes up to where I currently am (the dream-flashback scene in which the bridges are destroyed). So was it really necessary to use the second disk for a repeat of the entire movie but with the other ending, rather than adding that as an extra scene on the first disk, similar to how deleted scenes are typically handled? Maybe it would have created problems with viewers' sense of the story flow? It certainly would have left disk 2 free for the kinds of extras we would have liked to have seen.