What's the difference between the FMA and FMA Brotherhood series? I haven't watched Anime in many years, but recently I've had time to get back into it. I've seen that one of my favorite series, Fullmetal Alchemist, has done a series reboot.  What I'm wondering is:

Does it present a lot of deep variations (plot-wise, character-wise or otherwise), or is it just the same series with updated art?
There are a large number of differences between the two Fullmetal Alchemist anime, with far too many to list; therefore, I'll only cover the major ones.
To improve the flow of this answer, the following abbreviations will be used:
FMAM = Fullmetal Alchemist (Manga)
FMA03 = Fullmetal Alchemist 2003 (Anime)
FMAB = Fullmetal Alchemist Brotherhood (Anime)
The reason for the difference is because FMA03 was created when FMAM was still in the early stages of its development. When an anime series is based on a manga that is still in development, the anime is eventually going to reach a point where it outpaces the manga, because anime episodes tend to be developed quicker than manga volumes. When this happens, either filler for the anime is created or changes to the anime's storyline and characters are made so that the anime can continue to be developed. The latter is what happened to FMA03. FMA03's storyline started to diverge from FMAM's storyline after around 10 episodes because, at that point, the anime was starting to outpace the manga.
On the other hand, FMAB was created when FMAM was nearing the end of its development. This allowed FMAB's storyline to be more faithful to FMAM's storyline because FMAB had a mostly-complete storyline to draw from FMAM.
The major differences between FMA03 and FMAB &amp; FMAM are:
Storyline

 Although both stories follow Edward and Alphonse, the overarching story is considerably different between FMA03 and FMAB &amp; FMAM. In FMAB &amp; FMAM the main antagonist was a character referred to as Father, a being of incredible power who is capable of performing transmutation at will, and without regard for equivalent exchange. His ultimate goal in FMAB &amp; FMAM is to steal the power of what he refers to as &quot;God&quot; and become a being of infinite power and knowledge.
 The main antagonist in FMA03 is Dante. Unlike Father, she is just a normal human being who created a Philosopher's Stone and has managed to live a long time by transferring her consciousness into the body of other human beings whenever she was nearing death. Dante's only motivation is to become immortal and live forever.

The Homunculi

 In FMA03, the Homunculi were the result of attempting to perform human transmutation and failing. They could only be killed by destroying their original body.
 In FMAB &amp; FMAM, the Homunculi were created by Father, with each one representing a different aspect of his personality (Lust, Gluttony, Envy, Greed, Wrath, Sloth, and Pride; the seven deadly sins). Each Homunculus is also powered by a Philosopher's Stone. Unlike FMA03's Homunculi, FMAB &amp; FMAM's Homunculi do not have an &quot;original&quot; body that needs to be destroyed. Instead, either the Philosopher's Stone powering them needs to be destroyed or its power drained (normally through forcing them to regenerate  multiple times).
 Another difference is the identify of the Homunculi themselves, with some Homunculi from FMAB &amp; FMAM not appearing in FMA03 at all and others having their name changed.
 Gluttony, Envy, Lust, and Greed have the same name and appearance in FMAB, FMAM, and FMA03.
 FMAB &amp; FMAM's Wrath (King Bradley) is called Pride in FMA03.
 FMAB &amp; FMAM's Pride (Selim Bradley) is not present in FMA03.
 FMA03's Wrath is unique to the series. He was the result of Izumi Curtis's attempt to revive her son.
 FMAB &amp; FMAM's Sloth is not present in FMA03.
 FMA03's Sloth is unique to the series. She was the result of Ed and Al's attempt to bring back their mother.

Hohenheim

 In FMA03, Hohenheim is just a normal human being who was originally Dante's lover; however, he eventually left her due to no longer sharing her desire to have immortality at any cost. Like Dante, he created a Philosopher's Stone and gained a long life by transferring his consciousness into another person's body. His role in the anime is very minor, and he becomes trapped on the other side of the Gate after a confrontation with Dante that ended in failure.
 In FMAB &amp; FMAM, Hohenheim was a human Philosopher's Stone with a seemingly infinite supply of power. Although he was originally a slave, he was granted his near-immortality by Father well before the events of the series took place. Hohenheim is more significant in FMAB &amp; FMAM, facing off against Father at the end of the series. Unlike FMA03's Hohenheim, he dies at the end of FMAB &amp; FMAM after finally exhausting the power of his Philosopher's Stone.

The Gate

 The Gate is the largest major change in the series. In FMAB &amp; FMAM, the Gate is the source of all alchemy and also seems to be a source of infinite knowledge. The Gate is also guarded by a being commonly referred to as Truth, and who is responsible for taking the required tolls from alchemists who perform human transmutation. Those who are capable of performing alchemy have their own gate, and if that gate should be removed (by sacrificing it to Truth), they will no longer be able to perform alchemy.
 In FMA03, the Gate is still the source of alchemy, but it also serves as a portal between the world of Fullmetal Alchemist and Earth. Furthermore, the Gate derives its powers from the souls of those who have died on Earth and is what powers the transmutations performed by alchemists.