Boing Boing's Cory Doctorow's Charitable giving guide, the 2007 edition (complete list on Boing Boing) is a great example of finding interesting not-for-profits to donate to this holiday season. He suggests: Electronic Frontier Foundation, Creative Commons , Free Software Foundation/Defective By Design , and the The Internet Archive because he obviously loves the the tech/computer charities. Check out his list for the tech geek in your life.
Go to Heifer International to give a gift that is sure to start a conversation. Gifting a cow can do that.
Kiva.org is the gift that keeps on giving, as well as, the gift that keeps on letting you give. Give someone $25.00 to invest in pre-screened individuals whose lives can be radically changed by a micro-loan. The most amazing part happens when they pay you back. You can then re-loan your same investment to help another person.
Craft Site Directory has a whole page of Craft Charities.
Without a doubt there is a charity out there that your friend will thank you for donating to in their honor. And the best part is... is that they don't have to find room for it on their shelf.