I think it’s the potential fall out afterwards. Will losing the referendum, for example, cause a second go at Scottish independence? We know that Scotland is very pro EU, and will very likely not want to leave - this could potentially cause the break up of the UK. Will winning cause a massive fracture in the Conservative party, with the EuroSceptics creating a massive fuss that Cameron failed to support their views?
I can’t see Cameron’s position being that stable in either situation, really. He’ll have to reign in his party a lot whatever the result, I think.