We've been hearing a bunch of talk from the folks involved with Iron Man 3 that more movies are on the table. The story for the next sequel really comes down to what happens in Avengers 2. If Hulk does go crazy and has be banished from Earth (rumored plot point) perhaps Stark takes on the duty to find a habitable planet for his friend Bruce. Basically having Bruce and Tony going on an intergalactic road trip together. There are rumblings that there is a connection to the Guardians in Iron Man 3, so having Stark exploring space in the new films wouldn't be much of stretch. I would kind of love to see a buddy film with Bruce and Tony. Something that had been speculated during Avengers because of the budding bromance. If it did have elements from Planet Hulk story why not combine it into something fresh? Allowing them to use a cosmic villain that might eventually return to Earth for Avengers 3. While World War Hulk sounds awesome there are plenty of equally threatening villains to consider.
It's also possible that the film could stay earthbound and there are still a couple of angles the writers could go. A bit of conflict with the global energy crisis could see the Roxxon corporation which was been established twice already in the MCU. First with the final battle scene in Iron Man along with a Roxxon gas station in the short film A Funny Thing Happened On The Way To Thor's Hammer. So the company could end up becoming a bit of a threat to Stark and his fusion projects. Instead of just using his technology for weapons, destroying or stealing Tony's fusion technology to make themselves the largest supplier of energy on the planet. Exploiting it to their profits and eventually making them more powerful than any nation.
I've come up with a couple of villains that could end up used in Iron Man 4 or even Iron Man 5 depending on what angle Marvel decides on. While it's possible a few might be adjusted to be a little more cinematic than in the comics. We've heard that Marvel is over using men in suits as villains for the Iron Man franchise. So these suggestions seem to be inline with what the studio could be looking at for future installments.
ROXXON CORPORATION: The evil energy company owned by KGB Agent Aleksander Lukin has been used in multiple comics including Spider-Man and Captain America. They have been established in the MCU (first in Iron Man) and could make an excellent contrast from Advanced Idea Mechanics and might see the two combine resources. Instead of technology and weapons the company takes major interests in energy. One aspect of their interest with Stark Industries could be Stark's fusion technology. Selling it to criminal allies like A.I.M. and HYDRA to power their weapon systems or even space exploration ships (leading to the discovery of Red Skull?).
While Lukin is connected to the company it's very possible they might have him as the major villain in Captain America: The Winter Soldier. As he is the mastermind behind the Winter Soldier program but could be replaced with better known Captain American villains such as Baron Zemo. Roxxon has also employed supervillains such as Coldblood 7 (James Badge Dale plays him in Iron Man 3), Ghost and Serpent Squad (led by Red Skull's daughter). It's possible that another Marvel villain could end up heading up Roxxon besides Lukin.
COUNT LUCHINO NEFARIA: The Count is an Italian aristocratic villain that pocesses superhuman powers and founder of the Nerfaria Family of The Maggia. An international crime syndicate that is the world's most powerful organization dedicated to conventional crime (as opposed to subversive activities). Originating in southern Europe, the Maggia spread throughout non-Communist Europe and the Americas. Its presence in the United States first came to public attention in the 1890s, and the Maggia's widespread bootlegging of illegal liquor during the Prohibition Era has become legendary. Today the Maggia controls most of the illegal gambling, loan-sharking, and narcotics trade in the United States, as well as many legal gambling casinos in Atlantic City, New Jersey and Las Vegas, Nevada. It also has great influence within various labor unions, and controls politicians on every level of government. Especially in recent years, the Maggia has invested many of its illegal gains into legitimate businesses. However, the Maggia enforces a strict code of secrecy among its members, and does not hesitate to punish betrayals and failures with death. Often the Maggia marks one of its members for execution by having a Maggioso grasp the intended victim by the chin in the so-called "Maggia touch."
I could see Count Nefaria and The Maggia having ties or being the real people behind Roxxon. With the Count as the face of the company or at the very least pulling it's strings. Nefaria is an Avengers villain like Grim Reaper who is also involved with the Maggia.
WHITNEY FROST (MADAME MASQUE): Whitney Frost (Giulietta Nefaria) tries to gain access to Stark Industries weapons, secrets and other technology by exploiting S.H.I.E.L.D. Agent Jasper Sitwell. Maximiliano Hernández plays Jasper in Thor and Avengers so that aspect could be easily added. Like her father Count Nefaria is leader of crime syndicate The Maggia. Whitney has been mostly a conflicted Iron Man villain while wanting to contribute to her criminal organization she also has true feelings for Tony.
GHOST: On the Roxxon payroll (at times) the industrial thief is an anticapitalist saboteur who seeks to destroy various political and economic institutions he views as oppressive, apparently being most interested in those dealing with advanced technology and surveillance.
GREY GARGOYLE: French chemist Paul Pierre Duval is turned into the Grey Gargoyle after a chemical accident. It grants him the ability to turn anything he touches to stone. Duval has ties to A.I.M. and The Masters of Evil. He was apart of the villain lineup on the 90's Iron Man cartoon alongside Mandarin and Whiplash.