Nineteen-year-old Ryan Harrison reached his first ATP Tour semifinal, but ultimately fell to Fish who defeated Isner in a rematch of last year's final.
Despite being unseeded, Lu Yen-hsun and Ryan Harrison brought their good form from Atlanta to achieve consecutive quarterfinal appearances in the Series.
Playing her first tournament on American soil since 2009, Williams showed excellent form, serving bagels in her opening round match, and followed that win by upsetting Sharapova in the quarterfinals.
Atlanta champion, Mardy Fish, who also reached the final of the Farmers Classic, was forced to withdraw from the tournament, citing a bruised right heel.
Despite sustaining a shoulder injury earlier in the tournament, Agnieszka Radwańska was able to reach the final for the second consecutive year and defeat top-seed, Zvonareva, for the title.
Despite losing only six games en route to the semifinals, fourth seed, Victoria Azarenka, lost in straight sets to Stanford champion, Williams, who extended her win streak to ten matches.
The quarterfinals brought a pair of upsets as former world number ones, Rafael Nadal and Roger Federer, bowed out to Fish and Tomáš Berdych, respectively.
Neither player could follow up the win, and instead, Andy Murray handed Djokovic his second loss of the year after the world number one was forced to retire from the championship match.
Russians, Zvonareva and Sharapova, advanced to the semifinals without dropping a set, joining lower-seeded players, Andrea Petković and Jelena Janković in the final four.
Three-time defending champion, Caroline Wozniacki, and French Open finalists, Li Na and Francesca Schiavone, headlined the event.