We did three:
1) Disney honeymoon registry
2) Williams-Sonoma
3) Amazon.com
The Disney registry worked out much better than I had expected. The site has lots of issues, but people ended up giving us honeymoon stuff at our shower and for the wedding, to the tune of over $800! I wasn't sure if that registry would get used as much, but I think people enjoyed making little cards and graphics as part of their gift to tell us what they purchased from it.
Williams-Sonoma was picked because we'd already lived together for awhile and had a bunch of house stuff. I really wanted to upgrade my cookware, and W-S had what I wanted. Plus, they say it's good to have at least one 'brick and mortar' store for those who don't like to online shop.
Amazon.com was our catch-all. They offer a universal registry, which means that you can pick any item from any website and add it to your Amazon registry. This was such a good idea. I just added the link to my bookmarks bar, and anytime I came across a product on a website, I clicked the bookmark and it brought up a box and auto-entered the name of the item and the price. You could add notes to it if you wanted. This was the best way to add items from here and there that would never have been located in just one store. I highly recommend using this for anyone.
My advice is to stick with 3 registries and make sure one is an actual store. If you need a lot of basics for the home, Target and Bed Bath and Beyond are also good options, as are Crate + Barrel, Kohls, and Macy's. Again, we didn't choose those because we already had a place together (though we did receive a few gift cards to them). W-S was my specialty store, though others may choose stores like EMS if they are the outdoorsy type, or WineEnthusiast.com if you're a wine-y. The cool think about registries nowadays is how unique you can be -if you don't think you'll need 12 place settings of fine china, then you don't have to register for them! Have fun with it.