Anyone who is involved in a serious pursuit of science - especially cosmologists, astronomers, and physicists - has this same feeling of the inescapable insignificance. I'm not saying as a matter of reality that we are insignificant, but to feel that we might be the only significant thing in all of it strikes me as strange. To me, the normal reaction to discovering that the geocentric model is false and that we are part of a huge galaxy which is itself part of an infinite number of galaxies, etc etc should fill a person with a healthy sense of "wow, look at the vastness of the universe and how small we are in all of it." You're right that small doesn't mean insignificant, but the feeling of relative insignificance still seems inescapable to me and being small in the scheme of things is something that hits the emotions in a powerful way. The vastness of the universe should instill some humility I think.