I work in the nonprofit world, so I could give you hundreds of suggestions. Many worthy causes out there. I don't want to plug my agency on here, but if you want to give to your local AIDS organization, that would be great.
Also, I would suggest that people look at some of the charities in their backyards and get involved as a volunteer and donor. As they say, "Think Globally, Act Locally."
If I had to pick one not-for-profit on a national level, I would suggest giving to the Funding Exchange http://www.fex.org/
The Funding Exchange grants money to projects that are focused on changing the conditions of poverty and injustice. They give grants to a variety of projects throughout the United States. They work on a variety of social, economic, and environmental issues.