First of all: 500px is a photo portfolio site. You can create a page dedicated exclusively to your best shots, customize it to some degree, add contact details and even use your own domain name (if you’ve upgraed your account). So it is not something where you put all your vacation shots online to share with your family but more if you’re proud of one picture in particular.
In this sense it is quite similar to smugmug (except for the amount of customizing you can do) but with a stronger focus on the community. So this should bring it closer to Flickr but there are some big differences here as well:
For instance: Users on Flickr over the years organized themselves more and more into groups. A group, for those who don’t use Flickr, is mostly a forum combined with a photo pool where every member can share photos from their collection. 500px on the other hand doesn’t have something like that. All discussion is centered around the individual images.
And this is actually why I visit photo communities: The individual pictures; and I usually don’t discover them using some topic-specific group page but (1) by looking at pictures by people I follow and (2) by using some kind of “recently uploaded” page. While Flickr has both and has some problems with the first one as described by Timoni West, 500px does both two and the first one far better than Flickr by simply listing more pictures by your contacts ;-)
But the different focus really shows on the individual photo page. Beside the actual image the most prominent parts of the page are how popular it is and with what camera settings it was made if this information is available in the EXIF tags.
No listing of location, no separate group pools, just the absolute minimum. Ok, not on the same level as smugmug but pretty close :-)
500px also tries to integrate your gear into the whole photography experience. Sadly this is currently limited to only adding the type of your cameras, lenses and other gear using a simple text field. In this area I’d really love to see some kind of collaboration with a database-style site like gdgt. There is just too much information already out there not to use it if somehow possible :-)
I just started with 500px a couple of hours ago but I can definitely see myself using it in the future for sharing some of my best shots. My primary photo portfolio will still be on smugmug but 500px could replace Flickr for me in the future, especially if the level of quality on the “fresh page” stays that high :D