HopelesslyRomantic
Conquering the Milky Way is crazy enough (100,000-300,000 light years across 100 billion stars), but bringing in Andromeda (2.5 million light years) adds to the crazy. If we want a story where 25 worlds makes a prominent empire (so maybe the federation has 100, and the four know great powers 400 in all?), you only need a sphere 50-100 light years in radius, depending how common usable worlds are). There are 1800 stars within 50 of us, 60,000 within a hundred. That would leave the other 99.99999% of the Galaxy open to future plotlines.