Ok, so here's my plan:
Start a foundation. Set up multiple wings that each have different goals.
Wing 1: Small gifts
Similar to Micah's idea that spurred this, I would set aside a certain amount of money to be invested and then use the returns to fund giving small to medium one time donations to random people for random reasons. The goal would be to find situations where a small amount would lead to a large amount of short term happiness or stress reduction. Employees at the foundation would get an allowance from this fund where they could give to whoever they wanted. So if they met someone in line at the grocery store with a good story they could give them $100 or something and get reimbursed out of their fund. We'd also take suggestions and requests from people outside the organization (like when local radio stations have people call in and nominate other people to get free christmas gifts for their kids). Nowadays we could probably also go through the millions of gofundmes and find a bunch of people who fit the bill.
Wing 2: Lead
I'd want to invest in cleaning out lead based paint and have the goal of removing all significant sources of lead poisoning in various communities. I'd probably start in the U.S. (maybe Flint if there's room for more assistance) but would mostly look for places where the money could do the most good. Even if it meant tearing down large housing developments and building new ones I think it would be worth it and there would be ancillary benefits anyway.
Wing 3: Science
I'd have one section that gives money to research that needs funding. We would focus on replication and meta-analysis studies that clarify and hone scientific knowledge rather than make big discoveries. I'd be especially interested in funding something that tried to be a source for current scientific understanding with an emphasis on accuracy and a holistic point of view rather than give results of individual studies.
Wing 4: Other
I'd probably save some for just regular charities I'd give to anyway. See
this article for good examples. Something like
GiveDirectly is pretty similar to Wing 1 idea except it's international and helps people who are much more poor than most Americans.