Dropped!

Dhoom, Dhoom 2 and Dhoom 3
While the first Dhoom flick had John Abraham playing the antagonist, Esha Deol and Rimi Sen played the female leads. Dhoom 2 saw Hrithik replacing John and Esha and Rimi Sen dropped to include Aishwarya Rai and Bipasha Basu. Dhoom 3 saw Aamir instead of Hrithik and Katrina instead of Ash and Bipasha.

Race and Race 2
This 2008 Bollywood suspense thriller had actors Anil Kapoor, Saif Ali Khan, Akshaye Khanna, Bipasha Basu, Katrina Kaif and Sameera Reddy playing prominent roles. Race 2 saw Anil Kapoor and Saif Ali Khan reprising their roles. Bipasha, Akshaye and Sameera exited while Deepika Padukone, Jacqueline Fernandez, John Abraham and Ameesha Patel were added to the cast.

Munna Bhai MBBS and Lage Raho Munna Bhai
Gracy Singh was paired opposite Sanjay Dutt in this 2003 flick. However, in it's sequel, Lage Raho Munna Bhai, Gracy was replaced by Vidya Balan as the female lead.

Dabangg and Dabangg 2
Salman Khan's 2010 action blockbuster Dabangg had Sonu Sood play the villian to Salman's Chulbul Pandey. However, in it's sequel Dabangg 2, the role of the villain went to Prakash Raj.

Golmaal and Golmaal Returns
Rimi Sen played the female lead in the first film of the Golmaal franchise. However, she did not make it to the sequel. Kareena Kapoor and Amrita Arora replaced Sen in Golmaal Returns.

Masti and Grand Masti
In this 2004 comedy, Riteish Deshmukh was paired opposite Genelia D'Souza, Aftab Shivdasani with Tara Sharma and Vivek Oberoi opposite Amrita Arora. However, in the sequel while the main leads remained the same the female leads went to Karishma Tanna opposite Vivek, Manjari Fadnis opposite Aftab and Riteish opposite Sonalee Kulkarni.

Koi Mil Gaya and Krrish
Krrish, a superhero film released in 2006 with Hrithik Roshan, Priyanka Chopra, Rekha and Naseeruddin Shah in prominent roles. However, its prequel was another flick by a different name – Koi Mil Gaya – starring Hrithik Roshan, Rekha and Preity Zinta. Preity was only part of the first film. Subsequently, you saw Priyanka replace her in the sequel Krrish.

Hollywood did it too

Iron Man and The Avengers
Terrence Howard was reportedly the highest paid actor on the set of the first 'Iron Man' movie. But he was not part of any of the sequels. Howard was part of Iron Man (2008) but was replaced by Don Cheadle in Iron Man 2, Iron Man 3 and Avengers: Age of Ultron.

Batman
Various actors have played Batman. Michael Keaton starred in two movies directed by Tim Burton. Keaton was later replaced by Val Kilmer in the next movie. Kilmer was also replaced by George Clooney. And in 2005, Batman' got rebooted, with a trilogy directed by Christopher Nolan, and starring Christian Bale. Ben Affleck has since been cast as Batman in an upcoming film directed by Zack Snyder.

Spider-Man
Tobey Maguire starred in the trilogy directed by Sam Raimi, titled Spider-Man (2002), Spider-Man 2 (2004) and Spider-Man 3. While Andrew Garfield stars in the reboot directed by Marc Webb. It focuses more on Spider-Man's younger days, and includes the films The Amazing Spider-Man (2012), 'The Amazing Spider-Man 2 (2014), and The Amazing Spider-Man 3 (2016). Also, planned is The Amazing Spider-Man 4,' due out in 2018. But it's unclear whether Andrew Garfield will stay on for that movie.

Harry Potter Professor Dumbledore
Richard Harris played the much loved character of Professor Dumbledore in the first two Harry Potter movies - Sorcerer's Stone (2001) and Chamber of Secrets (2002). But he passed away a couple of weeks before the premiere of Chamber of Secrets. In the remaining Harry Potter films Dumbledore was played by actor Michael Gambon. The list of flicks include Prisoner of Azkaban (2004), Goblet of Fire (2005), Half-Blood Prince (2009), Deathly Hallows: Part 1 (2010) and Deathly Hallows: Part 2 (2011)

James Bond
There have been a number of James Bond' movies made over the years. And many different actors took on the lead role.
Sean Connery -- 'Dr No' (1962), 'From Russia with Love' (1963), 'Goldfinger' (1964), 'Thunderball' (1965), 'You Only Live Twice' (1967), 'Diamonds Are Forever' (1971)
George Lazenby -- 'On Her Majesty's Secret Service' (1969)
Roger Moore -- 'Live and Let Die' (1973), 'The Man with the Golden Gun' (1974), 'The Spy Who Loved Me' (1977), 'Moonraker' (1979), 'For Your Eyes Only' (1981), 'Octopussy' (1983), 'A View to a Kill' (1985)
Timothy Dalton -- 'The Living Daylights' (1987), 'Licence to Kill' (1989)
Pierce Brosnan -- 'GoldenEye' (1995), 'Tomorrow Never Dies' (1997), 'The World is Not Enough' (1999), 'Die Another Day' (2002)
Daniel Craig -- 'Casino Royale' (2006), 'Quantum of Solace' (2008), 'Skyfall' (2012)

The Hulk and The Avengers
Eric Bana played the lead in Hulk (2003), Edward Norton replaced him in The Incredible Hulk (2008), while Mark Ruffalo played the role in The Avengers' (2012) and Avengers: Age of Ultron (2015).