You can't quite kill everyone, because guards,as well as foes in the wild or in caves,ruins and such will spawn again every couple of days..so as it already said-you can't end the game.

Once you've finished all the quests in the game,which will probably take you a whole lot of time,and will be pretty boring ventually,you can start trying the thousands of mods the game have..some add weapons,armors,monsters,companions,missions and pretty much everything you might imagine added to the game.

However,I found the game quite boring when I've maxed my level(all major skills we're 100),even thought I haven't even played the main quest back then..because it feels really boring to wander around with nowhere to expand,and no real way to get better..