How is Pandemic Legacy impacted by playing with two characters?
The biggest spoiler-free Legacy-specific difference is probably in the end-game upgrades: if any given character gets half the player turns instead of a quarter, buffing a character becomes comparatively more powerful. By the same logic, the amount of damage a single Scar can do to a smaller team is greater. 

However I think the most important differences are the same as those of the base game (and are covered in this other question).