We just registered a .CO as the main address for our new startup. We think of it somewhat as a placeholder, as we hope to one day purchase the .COM since it's not actively in use by its current owner (but we haven't tried to contact yet). When we started, we had always called the product Rugby, but since the .COM is owned by Polo Ralph Lauren, Rugby.com would never be an option.
I think that had the .COM for our startup been taken by a pre-existing company with deep pockets and a strong brand, we would have simply chosen a different name. Incidentally, Rugby.co was already registered, and by a COLOMBIAN of all people. :)
We've all heard of sites that started with less-than-ideal domain names and upgraded when they had the money, and we rarely hear any of them complain about how much they spent.