1. Ben Sisko
Sisko set the character of the entire show. He wasn't scientific, diplomatic like Picard. He was a wartime commander, the 'Renegade' choice in Mass Effect. He could stare down a Klingon, he knew what he thought was right and did anything he had to do to achieve it, and nothing was sacred in the path of achieving that goal. And screw politicians. Seriously, screw them. Without him we don't have nearly as great a show.
The other character who couldn't be replaced and still have the same kind of show. Quark was the critic of the Federation that Gene Roddenberry would have cringed at. He called it on its conceits, and managed to be an opportunistic profiteer while still having a strong moral center when it's important. Quark was the character who made you think, maybe Federation progressiveness isn't all it's cracked up to be.
3. Kira Narys
A terrorist in a Starfleet crew, a paragon of loyalty without being apologetic for killing civilians and other Bajorans because it was the only way to defeat the common enemy. At times feels like she's more made for Battlestar Galactica than Star Trek. Without her the Bajoran wouldn't have felt quite the same.
4. Kai Winn
The perfect villain. The perfectly self interested 'True neutral' political figure who, in the face of Kira's pure spirituality, used spirituality for her own personal gain. But what made her great was her commitment to her character. She didn't think the school was blasphemy, but she was so fully committed to that self-serving angle it was hard not to believe she was.
5. Gul Dukat
Similar to Kai Winn except more violent, he's so perfectly able to sell his current story you almost forget it's all a political smokescreen for his true motives.
Morn definitely deserves a mention for 'Best non speaking character of all time'.
This topic has made me think about just how great the DS9 cast is. It's hard for me to leave Jadzia Dax, Worf, Garak or Odo out of any 'best character' list. Compared to TNG which had five amazing characters in Picard, Riker, Data, Worf and Q and then who else? If I had to name a 'Least favorite main character' in DS9, I'd have to say Bashir or Rom. But they were both characters I like, and so are Martok, Gowron, Eddington, O'Brien, Bareil, Shakaar, Zek. DS9 has by far the deepest cast out of any Trek.