Evil Genius. Such a great concept, I'm amazed it hasn't been revived up to this point. Same for Startopia.
A sequel to Master of Orion 2. Because as we all know, MOO3 NEVER HAPPENED.
No One Lives Forever. Set today. Kate Archer's Daughter (Granddaughter?) is the main character, and Kate provides mentorship and training.
Sword of the Samurai. With the success of CK2 and Shogun 2, I think this would be a huge hit.
I started playing Evil Genius again recently and it truly is a wonderful concept. I'd love to see someone make a sequel!