First off, it means that the search is now out for a replacement director. We'll be hearing the usual pie-in-the-sky names (James Cameron! Christopher Nolan! Terrence Malick!), but Marvel wants someone that they can exert a certain amount of control over. Still, star Robert Downey Jr. has director approval, and he is currently in a unique position of power. For all intents and purposes, Robert Downey Jr IS the Marvel Universe. Thor and Captain America may or may not break out, and if they don't, Marvel will have built their film universe on the foundation of a single actor, one whom they ironically didn't want in the project in the first place. Various people have tossed out Robert Downey Jr's name as a director for the third Iron Man picture, and it's not as crazy as it might seem. Point being, arguably the only person who can stand up to Marvel's Kevin Feige is Downey Jr, so having Downey Jr. at the helm is arguably the only way to actually make sure that Iron Man 3 is in fact an Iron Man film, and not a quasi-sequel to The Avengers, Thor, The Incredible Hulk, and Captain America.
But assuming that Downey doesn't want the gig and/or the studio won't give it to him, who should get it? The usual names are being tossed out (Neill Blomkamp, Guy Ritchie, Matt Reeves, etc) as well as a few slightly-off-the-beaten path choices (Shane Black, Peter Berg, etc). Assuming they don't go for a hail-Mary and snag someone like Kathryn Bigelow or Francis Ford Coppola (assuming they even want the gig), we're probably looking at someone like David Gordon Green. Ironically, just two years ago, discussing David Gordon Green as a theoretical director for a big-budget comic book adventure would have been a cheap joke ("from the director of George Washington, All the Real Girls, and Snow Angels comes... Iron Man 3!"). But the man who was once the next Terrence Malick has found a new niche with broad comedy, with The Pineapple Express and the upcoming Your Highness leading the way.
If you asked me, I'd hire John Singleton. Between Shaft and Four Brothers, Singleton is perhaps one of the best action directors working today who isn't named James Cameron, John Woo, or Martin Campbell. And while Downey can pretty much direct himself these days, and the rest of the returning cast can do whatever heavy lifting is required, and the script will be whatever the Marvel suits deem it to be. But the one place that Favreau's prior pictures lacked is pure action. From the overly cartoonish finale of Iron Man to the overly slapstick race-car fight in Iron Man 2, the series has generally failed as a genuinely exciting action vehicle. Assuming Luke Cage (which Singleton hopes to helm with Tyrese Gibson in the lead) stalls, Marvel could do worse than to snap Singleton right back into the Marvel playpen.
As for any greater meaning, there is little to be found beyond the usual studio politics. Marvel built their grand moviegoing dream on the performance of the first Iron Man and then proceeded to nitpick the sequel and its participants to death, to the critical and financial detriment of the franchise. Fox seems to have learned its lesson on the success of Avatar, more or less leaving Matthew Vaughn to his own devices with X-Men: First Class and bringing in Darren Aronofsky for The Wolverine. Paramount seems to be getting out of the tentpole game altogether, with only Transformers and Star Trek left in their wheelhouse. Warner Bros used to be a shining light of big-studio daring, but their micromanaging of Terminator Salvation, Clash of the Titans, and Edge of Darkness leaves a genuine fear that the 'Dream Factory' is no longer a place for artistic freedom if your name isn't Chris Nolan. But more than merely making Marvel a preeminent symbol for studios biting the hands that feed them, this move makes Iron Man just an ordinary franchise that lost its director after two movies. Jon Favreau is the new Bryan Singer/Tim Burton. We'll know soon enough who the next Joel Schumacher/Brett Ratner is going to be.