If you want to take the Most Challenging Challenge That Will Ever Challenge You, but are having trouble coming up with a charity to support, here are the top five that I support when I get a chance:
The Comic Book Legal Defense Fund
The CBLDF provides legal assistance for comic creators, sellers, readers, and others those whose First Amendment rights are threatened. If you like swag in exchange for your donation, the CBLDF website has T-shirts featuring popular comic characters, signed comics, art, and lots more.
An outgrowth of the Occupy movement, Rolling Jubilee buys debt for pennies on the dollar, just like many banks and collection agencies do. Instead of trying to collect the debt, along with usurious fees, they forgive the debt.
Doctors Without Borders
Doctors Without Borders provides medical care to people in need all over the world. You often hear about them after major natural disasters (like the earthquake in Haiti a few years ago), but they operate year-round in areas affected by war, disease outbreaks, disasters, or just lack of health care.
American Red Cross
I'm going to assume you know about the Red Cross.
Your Local Food Bank
You'll have to look up the details yourself, but if you live in America, there's a food bank that serves people in your area, and they need donations of food or cash. If you're in my neck of the woods, it's Paducah Cooperative Ministries. If you also happen to be a comic fan or gamer, Crash Comics is a drop-off point. If you don't have time to pick up food donations, drop some cash (even if it's just the change you have left over after you buy your comics) in the fish tank by the register.