I have not played many such games, but speaking from what I know of what makes a successful game, I know that there are three things Descent 4 (if they make it) should have:
1. A story that gives the player a good, wholesome role as the protagonist.
We know D4 is about the invasion of the virus and its true origin. This will be no trouble to the writers so long as the player is a GOOD GUY! Almost nobody who plays for the story wants to be evil.
2. The gameplay should further immerse the player.
One of the shortcomings that Descent could never quite bridge was that the inside of a cockpit, while flashy, was not very personal, nor the levels very epic. If the designers of D4 make the players interaction with the cockpit like in "Metroid prime" where one can look about the interior of his fighter at the displays, then the game can ensnare a lot of people who "just want to be in the thick of it."
3. Surprise us!
We know there's always room for new weapons, but the Virus is finally rearing it's ugly head, right? You have the potential to surprise the living stuffing out of us. These robots could develop organic tissue and acquire unorthodox weapons to shoot you down with and look like a nightmare from a dark fantasy. Destroyed ships could be reanimated by massive virus infestations and have the virus launching flying corpses of ships or bots. This is only the beginning if done right. I hold out for good weapons and have a few ideas myself, but If D4 can make us feel like we have to get out of that little cockpit and breathe... Then it can sell as an incredible game.
I'm not saying that what it has improved upon in the past has been good, but I recently noticed that the coming trend for console and computer games is stories. I think a proper script for this act will send it into a place of fame... like it's predecessors. I have high hopes and crossed fingers that this rather tall order can be met.