I think on a very long time scale, the direct manipulation of the gravitational force (within a single frame of reference) is the most significant discovery mankind has yet to make. This technology would change everything.

It would be the greatest enabler on our path toward becoming an interstellar species. It would also revolutionize life here on Earth. With the ability to manipulate gravity, everything from travel to manufacturing would be forever changed in similar ways that manipulating the electromagnetic force changed our world.

Gravity is the only fundamental force humans are unable to directly manipulate. Tackling that problem is the most fundamental and significant problem we have yet to solve.