There will never be anything like the 2003 Fullmetal Alchemist. It did something very different from anything else ever made.
First off is the way it was directed. The music sounds inspired by Classical Music which fits perfectly in a Fantasy .Most Fantasy settings have this huge epic Orchestra to back up it's setting which I find doesn't draw me into a Fantasy setting as a soundtrack with actual melody would. You can see that FMA-1 choreographs the animation to its music. I find a lot of Hollywood movies don't do this, instead it looks like the music is choreographed to the action on-screen instead. Not that there's anything wrong with Hollywood soundtracks but it seems like music in this format is just an after thought.
Fullmetal Alchemist has many themes that come into play as the story progresses such as Racism, War, Politics, Science, Religion, Death, To even Life itself. These themes and their morals may fly over your head during the first viewing but the more I think about what Fullmetal Alchemist was trying to tell me, the more it makes sense. Some people call FMA pretentious with no real morals, I say to them, please think back on the series. Alchemy is just one huge metaphor for Science. That right there should already be a huge hint.
So what FMA does differently than any other show I know, is actually really hard describe why I think this.
You would expect this show to a typical Shonen but it's not. It's a Fantasy epic, but not really. Unlike a lot of Epics like The Dark Knight or even FMA: Brotherhood, it's not a huge over the top epic with lot's of explosions and flashy attacks. FMA is more homely and humble than that, I remember one episode where it was almost just like a nice day, and a lot of early episodes of the first Fullmetal Alchemist either start or end like a nice day and it contrasts really well with some of the more darker moments making them a lot more tragic. I think the show is taking this mature story and putting it in the perspective of kids. In the second season, this Kid-friendly feel drops and becomes slightly more darker. This is great because things get more serious. The action builds up at this point but so does the story itself. FMA will surprise, shock, make you cry and even make you think.
Fullmetal Alchemist really impresses me, especially for a series that is 90% filler.