I would suggest that this would be an excellent time for Y Combinator to consult with Holden Karnofsky of Givewell, which has done a large amount of smart investigation into nonprofits. Karnofsky is local to the Bay Area.
Caveat: Givewell tends to focus attention on nonprofits with well-validated, very-high-probability, easily-quantifiable effects which is not where one would expect the greatest expected value from daring new attempts to be located. Nonetheless I would expect that talking to Givewell would be very epistemically profitable if you are just venturing out into the nonprofit space.
Caveat: Givewell tends to focus attention on nonprofits with well-validated, very-high-probability, easily-quantifiable effects which is not where one would expect the greatest expected value from daring new attempts to be located. Nonetheless I would expect that talking to Givewell would be very epistemically profitable if you are just venturing out into the nonprofit space.