After three seasons, there are a lot of unanswered questions, some going back to Season One. There are more than these, but answers to these questions would probably shed light on the answers to the others.
Note to Writers - enough already with ignoring plot lines mid-season, we want answers!
What is Rambaldi's endgame? How did Rambaldi make such accurate predictions?

What is the purpose of the following Rambaldi devices:The Circumference, The Sphere of Life?

Why was Rambaldi involved with bioweapons? Was that a means to an end, or an end in itself?

What are the meanings of Rambaldi's prophesies: Page 47 , and the one about The Chosen One and The Passenger destroying each other?

What really happened between Jack, Sloane, and Irina thirty years ago? Why is it necessary for Jack to keep Sloane alive, and for Sloane to keep Jack and Sydney alive? What relationship do they all have to Sydney and Nadia?
What really happened to Jack, Sloane, and Irina during Sydney's missing two years? Were there others in Sydney's close circle who had involvements in those two years that we don't know about?
Why didn't Sydney destroy The Cube instead of erasing her memories of the past two years? 
Why did Sloane hook up Jack to that IV at the end of Season Two?
Who is the head of the Covenant?
What was Lindsey's reason for wanting to kill Syd? What was on the blackmail paper he showed Sloane?
And the number one question - why do they show in each episode the top of the building that was the focus point of the alien's LA blast in Independence Day? Are they trying to tell us aliens are involved? Is it true that Rambaldi is an alien, and also Mac compatible? So is the 'greatest power' the Chosen One is suppose to destroy really Microsoft?


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