I finally got around to playing this game, and I usually enjoy a game with a good story. For whatever reason I can't seem to follow this story at all. It's like all they do is throw these names around and expect you to know who these people are.
I find I'm just going through the motions of playing the game without much in the way of story. 
I'd only say that i'm about 25% through but I have no idea what's going on.

Is it the flood of historical figures that is confusing or the Desmond Miles story that is confusing?

Medici: the good guys.
Everyone you shiv: bad guys.

Ya if you're really interested in the story while you're in the Animus you can check it out somewhere on wiki.  But in the end it's all about what's going on with Desmond.

Good to know. Yeah they just throw all these random characters at you. It's like I go to a way point and Ezio says he's after "xyz" guy and I"m sitting there trying to figure out who that character is/what they did/why I got to kill them

Do you read the database entries as they appear in game? They should give you the heads up on any character when they are introduced.

" @Scapegoat: ............no i don't.........food for thought though. "

Try using the codex (is that what it's called) they're narrated, the important ones even come with cool little cutscenes, they'll totally keep you up to date. 

Some characters are based on real life history.   Rodrigo Borgia is basically the enemy here.  If you read some history on him.  You would know how corrupt his family was and many films and stories like Godfather was based on his family.   Assasin's Creed 2 just puts a different spin on this history and at the same time tries to connect how these pieces of Eden make people so powerful in historical context.   Then there's the ending which will blow your brain out.   i won't spoil it.