I would keep Sigma as the antagonist. He's too integral to each game to omit. However, he does need more focus and better characterization instead of just appearing at the end as the obligatory final boss. Irregular Hunter X was a step in the right direction.
That said, focus and characterization is one of the biggest issues with the whole of the X-series. X needs more attention as the main character of all games, perhaps taking some ideas from Iwamoto, whereas Zero needs more attention in X3 for his upcoming role as an antagonist. It's just weird how the most virus-centric story does not involve the red one at all.
Other than that, the whole Wily - Zero - Virus matter needs to be explained in great detail in those respective games. Dr. Light could also stand to have a more active role in informing X about the situation.