Assuming Stark follows a similar path as Pym after Ultron, where he basically has to retire, he'll just be getting started up again in Iron Man 4, which will go well with a recast, imho, and just the overall theme.
Originally Posted by Lord
Is there any other storyline to take from?
Iron Man 1 adapted the Origin + Iron Monger storyline + Inpiration from Extremis
Iron Man 2 introduced elements from armor wars
Iron Man 3 adapted Extremis
I think you can do Doomquest-ishness, you'd just end up using someone like Count Nefaria instead, changing his power from something derived from some kind of 'nanotech suit' especially if he passed it off as innate power, and Iron Man was simply figuring out the 'hoax.' I'm also not sold entirely on 'Camelot' as a viable setting for a superhero movie, but some other time/reality shenanigans could easily take place.
You can also introduce Whitney Frost/Madame Masque through her father that way as a love interest and villain, presuming that even if Paltrow would come back that she wouldn't be played by the same actress, and the chemistry and power of that relationship would be lost with these new people stepping into those roles, so better to go a different direction.
So NefariaQuest, basically, as close to Doomquest as Iron Man 2 was to Armor Wars. You'll probably need to throw in some Stark disassembled as you build up the new guy to be the new Tony Stark.
Before of after that you could do a film about Ezekiel Stane with The Five Nightmares as he reverse engineers Stark Tech, and himself, and throws in elements from the recent 'Beleive' arc in there too.
After that though, you start to run out of original elements for these guys. Some modified take on Demon in a Bottle, where purhaps the substance is a bit more or a macguffin than plain old alcohol... that could be interesting.