I love Naughty Dog because they always try different things, and always succeed. I don't want them to get stuck in a franchise, even though I love Uncharted. Sometimes it's better to end with class, and try something new after that. 

Uncharted, imo, could be the perfect example of a declining franchise if they go too far. Uncharted 4 will be amazing (my opinion), but I honestly think it has to stop there, so the franchise will just be remembered for being awesome.

Naughty dog have said time and time again (including in the interview this was taken from) that they only work on projects that inspire them. They currently have 'over' 4 projects in the works, so it's doubtful that another Uncharted would in any way stop them innovating with a new franchise if they so wished. I want to see what this tease by Keighley was referring to:

But I'd still be happy to buy another Uncharted game if the opportunity arose .

True, even if they made 6 Uncharted games, they would make them for the right reasons, and surprise us each time.

Oh man, can you imagine a Sci-Fi game by Naughty Dog ? That would be GOTG material.