If given another shot, it sounds like Lawrence would’ve simply stuck to what worked in the text.
I Am Legend was generally faithful to the source material in the sense that it focused its story on a character named Robert Neville (Will Smith) dealing with his status as the last man on Earth.
However, the film made a number of notable changes to the source material, not the least of which included changing the vampires to zombie-like monsters, and turning Neville into an expert scientist with a legitimate shot at curing the disease.
Looking back, Francis Lawrence seems to think that audiences would’ve responded better to the film if it had stuck to the novella and told an arguably more straightforward siege story about a far more average man fighting an army of semi-intelligent vampires.