It can be enjoyed as a typical romantic comedy.
It can be enjoyed as an essential part of Nora Ephron's oeuvre as an auteur. It has got the Ephron-esque combination of quirkiness and melancholia and it is rich with her typical motifs, such as the daily presence of dead loved ones and a strong connection between two people who have never met (compare it with Sleepless in Seattle (1993) and Julie & Julia (2009) for example). It is also filled with links, puns and references to older films, besides being a remake of Lubitsch's magnificent The Shop Around the Corner (1940).
And it is also a good, mature sociological study of city life in an era of neoliberal policies and the corporisation of the city landscape. The changes are hard and uncomfortable, but unfortunately often inevitable, and after we've fought and lost against the force of time, we must mourn and move on.
You've Got Mail can be appreciated on each of these levels, independently of the others, should you so wish, but combined they make the film so much richer.
So have a look if you haven't seen it before. As an example, here's a good scene (that won't embed).
--------------------------------------------------
I've written about Nora Ephron before, with focus on Julie & Julia: http://fredrikonfilm.blogspot.com/2009/10/nora-and-meryl.html