For the human race: Safe water, war, climate change, and better access to space are probably on the list. The insane US political climate might be up there, too.

For us on HN: Anything that you can do to make a dent in any of the above problems. Also, internet security is completely broken and needs a total re-think and re-do. We need safe access to the world's information for the several billion people who are not yet online. (For that matter, we need safe access for everyone else, too.)