Novak Djokovic has already won the Australian Open, French Open and Wimbledon this year and is looking to complete the calendar-year Grand Slam with a US Open title so he will be extra motivated. The Grand Slams bring out the best in Djokovic and he is especially tough to beat in five set matches so whoever plays against him will have his hands full.
Alexander Zverev has had a good year. He got his first win on clay against Rafael Nadal at the Mutua Madrid Open earlier this year and beat Djokovic at the Olympics in Tokyo en route to winning the gold medal. He then went on to win an ATP Masters 1000 title at the Western & Southern Open in Cincinnati. Zverev can definitely cause problems for Djokovic at the US Open. He got to the finals of the US Open last year and has a legit shot at winning it this year.
Stefanos Tsitsipas had a great clay court season this year and got to the finals of the French Open but he hasn't had any notable results since then. Even so we expect him to bring out his best tennis at the US Open and reestablish himself.
Daniil Medvedev doens't play the prettiest tennis but he gets the job done in terms of winning matches. He won an ATP Masters 1000 title at the National Bank Open in Toronto in mid August and will be ready to go at the US Open.
Andrey Rublev won five ATP titles last year and one this year but he hasn't had great results in the Grand Slams. Even so compared to the rest of the field he has a better shot of doing well at the US Open. Just recently he got the win over Medvedev in Cincinnati and he'll be feeling better about his chances heading into the US Open.