Folding@home - help scientists cure diseases that have killed millions with your computer by running simulations for them (it's very easy to set up)
Video Game History Foundation - support video game preservation. "less than 3 percent of games released before 1985 are still in print" and it's not much better from 1985-2013." the history of this incredible art form is disappearing
The Blue Card - help Holocaust survivors living in poverty. 78% have difficulty performing daily activities such as dressing, washing, and cooking
Signal - message and call people privately and securely without worry of government censorship or any other creeps
Blind Cat Rescue - help blind cats who were deemed not adoptable by regular shelters and were going to be euthanized because they were blind
The Survivor Mitzvah Project - similar to The Blue Card above
Life After Hate - help people leave violent extremist hate groups