DonorsChoose.org
A new way to give to education - We've had several of our teacher friends call and tell us about this site. It is a way to give to approved school projects and help schools across the country. It is also a site where schools can submit a project that needs funding (books, special programs, etc...).
JustGive.org
They do both volunteer and giving on this site, as well. However, they also have some unique approaches to giving, like wedding registry and gift certificates, worth a look.
SixDegrees.org
This is Kevin Bacon's site and it is a wonderful way to pull social networking into the giving equation. You can see different charities your favorite celebs support and you can add your own, as well. You will also notice that their volunteer and donation engine is Network For Good.