Sources suggest that Iron Man, Captain America, and the rest of the Avengers could be coming together to fight shape-shifting lizards from space.
According to Iron Man director John Favreau, Joss Whedon isn't entirely sure what the Avengers movie is going to be about. The Albuquerque Journal, on the other hand, seems to have the inside scoop.
In an article about the movie filming in the city for six months, the paper casually included the line "The Avengers' script will blend Iron Man, Thor, and Captain America: The First Avenger story lines as the Avengers battle with two alien races, the Skrulls and the Kree." There's no source for this information, and the paper doesn't expand on it further, but it has been confirmed that a Skrull artifact will play some part in the Captain America movie, so there's a chance that this is true.
In the comics, the human-looking Kree and the shape-shifting Skrulls have been at war for millions of years, and both sides consider the Earth an important strategic location. As the Journal notes, the Thor and Captain America movies set up the events of the Avengers movies, so there's no reason the idea of an alien war can't be introduced in advance. It would also be a threat big enough to bring the various heroes together as part of Nick Fury's Avengers Initiative.
In the comics, however, the Kree and Skrull plans for Earth tend to revolve around clandestine actions and infiltration, rather than outright conflict, which might be a little too subtle for a two-hour blockbuster, unless it got quite simplified and streamlined fairly significantly. Not to mention that there are all kinds of terrestrial foes that could just as easily provide the Avengers with a challenge.
The Avengers movies doesn't come out until 2012, so we won't know for sure until then, but with any luck, we'll get some pretty big clues when the Thor and Captain America movies come out next summer.
UPDATE: According to Superhero Hype, the line about the Avengers battling alien races in the upcoming movie did not come from Marvel, and was apparently a "research error" on the part of the Albuquerque Journal. This doesn't mean that the Skrulls and the Kree can't appear in the movie, but there's nothing to suggest that they will anymore.