Differences
Most people believe that Fullmetal Alchemist: Brotherhood is the second season of Fullmetal Alchemist, but it's not. Brotherhood is a seperate entity; you should think of it as if the original Fullmetal Alchemist series didn't exist at all. Brotherhood focuses more closely on the manga storyline. During the making of the original series, they had to go off on a separate story line after so many episodes because there wasn't enough story in the manga series to draw from at the time.
The most important difference are the cast of the homunculus. In the original series, Wrath was Izumi's son. In the manga, Wrath is actually the Fuhrer, whereas the Fuhrer was Pride in the original. Sloth and Pride are also different. A new batch of characters are also introduced in Brotherhood, including a different alchemy technique that originated from a different country.