I'd love to see a biopic on Martin Luther King Jr, played by Zach Galifianakis, with an impassioned director(s) (hopefully Friedberg and Seltzer) defending him as 'the only man who could portray him', just to see if society as we know it would collapse.
Moving on from that, did you know Will Smith was considered for the role of Neo in the Matrix. Say what you will about Keanu 'balsa wood cut-out' Reeves, but the whole spaced-out thing worked in that film, and Will Smith (1999 Will Smith that is, still seen as the Fresh Prince, between Men in Black and Wild Wild West, soon to release 'Willenium') joking through the whole thing, getting jiggy with Morpheus, and bringing in dollops of cheese would've ruined it. . . a whole 4 years before the sequels did.
I was also going to mention Steven Segal trying to create a Genghis Kahn movie, with him as the lead, but won't go much further, because honestly, while that is a terrible idea, even if you have the best idea in the world, adding the words 'starring Steven Segal' instantly creates a bad film.