Give Directly and Against Malaria are two of the most effective charities in fighting global poverty and unneeded gifts. So little money (to Americans) goes such a long way there, and ethically I think it makes the most sense to put your charitable dollars in that arena. Maximum impact is always going to mean global giving.
.....that said, we give lots of money to domestic causes, which I don't really think are quite as defensible from a philosophical standpoint but it makes me feel a little better about the fact that my country's policies & politics bum me out on a daily basis. Give Directly and Against Malaria combined get half of our charitable dollars, but the other half go to Southern Poverty Law Center, Equal Justice Initiative, Planned Parenthood - and then also a local charity that provides health care & resources to homeless in my city, because I don't want to ignore my own backyard.
And right now I'm dealing with seasonal depression (come back soon sun?), so I'm about to place an Amazon order to send some needed things over to our local women's shelter, because sometimes giving THINGS feels better than giving dollars, even though that's not very logical.