First, a classic: Medecins Sans Frontieres (Doctors Without Borders). I don't know what I can add to what most people already know about MSF - if I was smarter and gutsier, I'd be doing something worthwhile with my life like working for them. They go into dangerous places and give people medical care. That's pretty bad-ass.
I've also given money to Apopo, the mine-clearing-rats place that Melissa mentioned in her last post.
One that bears special mention, I think, is Catholic Relief Services. I don't agree with everything they stand for, but they do a lot of very good work and they're my go-to charity when I'm thinking about my Catholic family. We're not going to agree on abortion any time soon, but CRS instantiates what I think is the noblest part of the Catholic doctrine: concern for the poor and marginalized.
I also feel like I should mention one that works directly with people here in my own community, which has problems of its own. Project Plase helps homeless people in Baltimore transition from the streets.