There is certainly more space than mass
About 400 billions stars in the Milky Way galaxy, so the Alpha Quadrant would have somewhere around 100 billion. Earth (and Vulcan and Q'onos) are all located in rather sleepy backwaters, where the lack of intense stellar activity lends itself to long periods of relative peace in which intelligent life could develop. The denser star areas could hide any number of life-sustaining environments, but might not be candidates for intense SETI for that reason. We're on the slow-moving Ferris Wheel. They're on the roller-coaster of death.
It would therefore be logical that any new, Alpha Quadrant civilization would also have developed completely different space and energy technologies. That would be the only way to explain how the trekverse hasn't run into them by the 25th century.
That and any number of civilizations that are nearing the brink of FTL. However, I suspect Babylon 5 had it right - you would find more dead civilizations than living ones. And their technology could be very dangerous to handle.
I like the idea of different space and energy technologies - so alien that they're almost indistinguishable from natural (non-artificial) phenomena. So far, SETI hasn't turned up much. There's talk about the Great Filter, but the filter might actually be more about us not having a clue what we're looking for. Alien life could be so alien that we have trouble identifying it as life, much less figuring out if it's intelligent.
Thanks!! rbs