Nadal has the toughest draw by far. Having Kygrios in R4, Thiem in Q4 and Medvedev in SF - has to be the three toughest possible matches in a row. Even if he gets through one, it creates more wear for the next one and so on. Obviously, if he gets through them all, he will definitely be battered physically - considering these could be three 5 setters in a row. So a UsOpen 2018 type situation for Nadal where he succumbs to injury.
That being said , Novak Djokovic should send Rafa a belated holiday present. Nadal has a MUCH BETTER record against the new gen players than Novak does. And it seems in having Thiem, Medvedev and even Stan on his side of the draw, Rafa's made Novak's job much easier.
The disparity in records is quite stark. Nadal is 21-8 and Djokovic is 12-10 in h2h with the next gen players below.
So while Rafa struggles against Novak, he handles the potential threats to Novak far better than the Serb himself does.
Nadal
Thiem: 9-4
Krygios: 4-3
Medvedev: 3-0
Tsitsipas: 5-1
Overall: 21-8
Djokovic
Thiem: 6-4
Kyrgios: 0-2
Medvedev: 4-2
Tsitsipas: 2-2
Overall: 12- 10