With his appearance in Disney+'s She-Hulk on the horizon and questions about his cameo in Shang-Chi lingering, Mark Ruffalo's Bruce Banner remains an important player in the Marvel Cinematic Universe. Ruffalo has played the role for so long that it's easy to forget he didn't originate the role in the MCU.
Edward Norton played Banner in 2008's The Incredible Hulk. Norton left the franchise before the Hulk joined the Avengers, partially due to his interest in work outside of franchise films. While Norton and his replacement were known for their work outside of genre fiction, an actor who played an iconic sci-fi role was nearly cast to play Banner instead -- The X-Files' David Duchovny.
Norton and Duchovny were the names on Marvel Studios' short-list to play Banner in The Incredible Hulk. Ironically, director Louis Leterrier's suggestion of Ruffalo was shot down by the studio because of his reputation as a serious actor, without much genre experience. According to Leterrier, Norton appealed to Marvel Studios because he was "more famous" than Ruffalo.
Part of Duchovny's appeal was the legion of fans he gained from his original, seven-and-a-half season and a movie run as Fox Mulder on The X-Files. Marvel Studios was enthusiastic enough about the prospect of Duchovny playing Banner that he outlasted actors like Johnny Depp and future Oscar-winning Joker Joaquin Phoenix in the casting process.
Marvel Studios was so interested in Duchovny that they were willing to work around his shooting schedule on his X-Files return. The 2008 film I Want To Believe was filmed at the same time as Incredible Hulk. Both films were shot in Canada. Unless he was going to pull some impressive double duty, Incredible Hulk's production would have been delayed to accommodate Duchovny.
Norton ultimately won the role, and being more of a movie star than Duchovny likely helped. He had been in crowd-pleasing mainstream movies like The Italian Job and Rounders in addition to his more "serious" roles. Norton's interest in the character may have also tilted the scales in his favor. Norton is a Hulk fan. He passed on the role in Ang Lee's Hulk because he didn't think it did the character justice. He had a clear vision for his Hulk, making script revisions during shooting.
Norton's passion for the character is one of the reasons that he clashed with Marvel Studios. They wouldn't have had that problem with Duchovny. Despite his status as a sci-fi icon, the genre leaves him cold. He's specifically said that he's "not a superhero comic book guy" in interviews. Duchovny's lack of fandom may have made for smoother sailing on The Incredible Hulk's set but may have left him uninterested in reprising the role in The Avengers and the rest of the MCU.
Had things worked out differently, Duchovny might be gearing up to appear alongside Tatiana Maslany in She-Hulk. It's interesting to think about what Duchovny would have brought to the role of Banner and the Hulk if had he taken the part. As disappointing as it might be for fans of the actor and the MCU, it might have deprived his most ardent fanbase of his X-Files return. Duchovny may have also been recast after one outing like Norton. It's a tantalizing What If...?, but one that won't be adapted on Disney+.