Some questions from my end:
1.) For the main story campaign, all Star Control games had a "Doomsday" counter. If too much in-game time passes the main story would end in failure. While I personally believe that this is an aged mechanic and players should be free to finish the game at their leisure, it is an important question to ask.
2.) Like Skyrim, will players be able to continue once the main story is complete?
3.) Are there randomly generated events/encounters that start and complete regardless of player participation? For an example of what I am talking about, the MMO Guildwars 2 has looping events that start and complete with or without player interaction, players can take party in these events to influence to outcome. Will a similar mechanic be in place in SC:O?
4.) Will there be unique alien captains that have a personality that is different from other members of their race (e.g. Talana and Captain Fwiffo in SC2)? Will you be able to form friendships/relationships/rivalries with these captains based on your dialogue choices an game progression (similar to Mass Effect companions or KOTOR party members). Will these captains react to or have special dialogue for story events? If this does not occur, it should.
5.) Will there be a hard or challenge area that unlocks after the game is complete? Say a section of space with extremely powerful but mysterious enemies that you can barely get past using the most powerful ship upgrades and fleet. This would be nifty to add.
6.) Will the main story follow a set chronological path or will you be able to complete parts of it independently and out of order. Will the order that you finish events in change or impact story?
7.) How in depth with the aesthetic customization of the flagship be? Can I paint it neon green to look like a tye-dye hippie out of woodstock?
8.) Will there be multiple endings based on your choice? Can you side with the bad guys?
9.) Will there be hidden stars that do not show up on the starmap but are visitable? (There should)
10.) Will there be some kind of cute/handsome alien or spiritual successor to the Syreen?
11.) Will there be a hollow planet with some kind of secret inside that you can find with a lander (giant technopolis, etc.)?