I'm running 308s in a smaller room so you certainly could. As for which to use i would say it depends on the genre you will be mixing. I am using a sub with my setup to be able to get a better idea of the very bottom but i know a lot of peeps dont use a sub with the 308. On the other hand , the 305 and 306 benefit more from a sub. The smaller will be loud enough for the new room setup IMHO, just low frequency light. They are very different from consumer speakers as far as imaging,etc. , so be ready for a learning process no matter which you choose. A lot of time spent listening to commercial releases that you know well will be in order.