What (or who) Could Keep Serena From Winning the Grand Slam?

Nerves:  If the end of her Wimbledon finals match is any indication, Serena will be nervous in New York.  She looked to be running away with the second set, but a patch of nervous play allowed Muguruza to get back in the match (albeit briefly).  If she got tight at this stage, it's possible she gets even more nervous when faced with the pressure of completing the calendar grand slam.  (She also tightened up in the French Open final against Safarova).  It didn't end up costing her at Wimbledon, as Muguruza was just as nervous as she was.  But if she's playing a more experienced player in the later stages of the US Open and succumbs to her nerves, she might not get off so easy.

A top player who finds "the zone":  Serena's usually so much better than everyone else that it doesn't matter if her opponent is having a particularly good day.  But there are a couple of players who could trouble her if they get in the zone for a day.  World number two Petra Kvitova has already beaten Serena this year in straight sets on her worst surface, and may finally believe she has what it takes to beat Serena.  Victoria Azarenka has been slowly rounding back into form after missing much of 2014 with injuries.  She's already taken Serena to three sets three times in 2015, and may be fully back in shape by the time the end of the hard court season rolls around.  If Azarenka keeps gaining momentum throughout the next month or two, she could be a very dangerous opponent.  It would certainly take an excellent performance by Kvitova or Azarenka to actually pull the upset.  But it's conceivable that if Serena comes out flat and they find the zone for a long enough stretch, they just might be able to get it done.

A dangerous early or mid round opponent:  When Serena loses in a grand slam, it's usually before the semifinals.  In 2013 her grand slam losses came to Sloane Stephens (Australian Open quarters) and Sabine Lisicki (Wimbledon Round of 16).  In 2014 she lost to Ana Ivanovic (Australian Open Round of 16), Garbine Muguruza (French Open second round) and Alize Cornet (Wimbledon third round).  Thus, if she's going to lose in New York, it looks like it's as likely to happen in the early to mid rounds as it is in the semifinals or finals.  It's hard to say why she loses more in early rounds than late, but maybe her focus isn't always as good against lower ranked opponents early on.  With so much on the line it's unlikely she'll overlook anyone, but if history is any guide surviving week one will be the key or Serena. 

Injury/playing with wooden racquet/ giving opponents the doubles alleys:  Maybe Serena rolls an ankle Sloan Stephens style and isn't able to play at full strength.  Or maybe she comes into New York playing with a wooden racquet because she decides she needs a real challenge.  If the US Open decides to give Serena's opponents the doubles alleys to make matches more competitive...well that still probably wouldn't matter.  But seriously, there is always a risk of some fluke injury slowing her down, and nothing should be taken for granted. 

Prediction:  It won't come without drama, but expect Serena to capture the Grand Slam.  She'll likely drop some sets along the way as she did at the French Open and Wimbledon, but should be able to manage her nerves just enough to avoid an upset.  Let's just hope the rest of the field rises up and doesn't let her coast to the title, as it would be great TV if she's in a tight third set battle in the semis or finals.