I like how Sins of a Solar Empire was the biggest space strat named. One mention of MoO. People just don't know strategy games, I guess. Going for the games where you can raze entire planets in the same way other strategy games raze cities (if you said total war you are WRONG) was the right idea, but Sins and MoO are on the small side as far as that goes.
I have to revise my statement on SotS though. While in that, and indeed sins and MoO you can run around destroying 'theoretical' galaxies, you won't. You'll play on a tiny ass map with a few hundred planets at best.
But there is one game where the destruction of a galaxy does happen. In one of the endings of Total Annihilation, the winning side literally collapses the entire galaxy (of which most had been colonized) and creates a new one. That amounts to quadrillions if not many, many more deaths. Quintillion? Sextillion? I don't know, the scale of a real galaxy is just mind boggling. So, that has to take the cake hands down.