Agreed with the sentiments so far. A direct sequel would probably diminish the original. But I have a feeling Naughty Dog could probably surprise us all and pull it off somehow. But I think it'd be better left alone and do like has been suggested, unrelated side stories elsewhere in a different time or something

But on that note, every time I hear about Dreamworks doing a sequel to an animated movie I liked, I always groan, and then it turns out surprisingly good in the end. So yeah, I don't approve, but I do have faith. If you're going to do it, do it well, and that's kind of their way of making games. Always trying to outdo themselves. So I don't think I'd sweat it, if they did