Same Role, Different Actor

[Chainsawmidget]

This was Harvey Dent in Batman.



This is Harvey Dent after getting splashed with acid and becoming Two-Face in Batman Forever.



That's gotta be some pretty damn powerful acid to turn Billy Dee Williams into Tommy Lee Jones. 

[Ash]

The National Lampoon Vacation movies have had several different actors play the Griswold kids.

[Mr. DS]

They replaced the first Jennifer in Back To The Future with Eliazabeth Shue in the sequels.  I think Crispin Glover was replaced for the small George McFly cameo in part 3.

[ulthar]

In the HUNT FOR RED OCTOBER, Alec Baldwin played the role of Jack Ryan. Harrison Ford took over the role of Jack Ryan in CLEAR AND PRESENT DANGER and PATRIOT GAMES.

And Ben Affleck in THE SUM OF ALL FEARS.

The Ryan series is quite full of switch-a-roos.  Here are but a few (major recurring characters from the books):

Cathy Ryan: Gates McFadden in HFRO, Anne Archer in PG and CAPD, and she was not present in SOAF.

John Clark: Willem Defoe in CAPD, Liev Schreiber in SOAF.

Judge Moore:  Ryan Reinhardt in HFRO, Dean Jones in CAPD.

(not listing Sally Ryan, since it is not uncommon for children to be played by different actors, especially to show time has passed).

[Mr. DS]

Julianne Moore replaced Jodie Foster as Clarice in Silence Of The Lambs. 

[Chainsawmidget]

Oooh.  I found the mother load of switches.  The Witchcraft series. 

Check it out.
http://www.obscurehorror.com/witchcraftime.html

Not only do they constantly change actors, they changed the lead Character's name for a movie before changing it back and changed the gender of another major character. 

[Doggett]

Robert Burke took over from Peter Weller in Robocop 3

[ulthar]

Julianne Moore replaced Jodie Foster as Clarice in Silence Of The Lambs.  

Speaking of SILENCE OF THE LAMBS, Jack Crawford was played by three different actors:

MANHUNTER:  Dennis Farina
SOTL: Scott Glenn
RED DRAGON: Harvey Keitel

[Hammock Rider]

  In Iron Man the role of James RHodes was played by Terrence Howard. In Iron Man 2 it was played by Don Cheadle.

[ChaosTheory]

Julianne Moore replaced Jodie Foster as Clarice in Silence Of The Lambs.  

Speaking of SILENCE OF THE LAMBS, Jack Crawford was played by three different actors:

MANHUNTER:  Dennis Farina
SOTL: Scott Glenn
RED DRAGON: Harvey Keitel

Hannibal was also played by a different actor in Manhunter.  Although maybe that doesn't count since Red Dragon was sort of a remake of Manhunter.