As far as I can see, there are three problems in this genre that have been very long running:
Fairness - most current games allow 'skips' in return for real money. This gives the impression others can be absolutely OP and just stomp anyone who's free playing.
Time played, even without the ten different currencies that you can convert from real money - someone coming into an online world will inevitably get stomped by someone with a year or two's experience in the game.
Things to do while waiting for building/ships/probes/etc
Case examples of attempts to solve over the years (mobile and PC):
Clash Of Clans - made an attack not devastating at all, cheapens the game and makes a lot of players question why they're playing at all.
Different servers, ogame-style. This separates people by time but inevitably the current server goes 'stale' and the veterans are forced to move servers, losing all progress in the process. Still has 'skips'
NPCs controlling the galaxy, you can choose to attack other players but the game prefers you to band together and go against the NPC
I'd like to hear your thoughts on how this genre can be improved upon, some ideas I've had spinning around my head:
Most of these games put you in the seat of a 'king' or ruler, what if we could take the good bits of these games and build something new? You're no longer the ruler, you're now a military commander aboard a capital ship with a set of advisory staff. You can advise the NPC ruler, it's his/her choice whether to follow your advice. You have full control over war and defense (the 'good bits')
You own a 'node' (region, plot of land, starsystem, etc - on a higher design level this doesn't matter yet) by placing an outpost in it. Outposts can be autonomous, controlled by the ruler, or controlled by you/the military.
Civil war is a possibility, if you and your ruler come into a heated discussion. You can depose him but it would have you battling it out and losing a lot yourself - if you're defeated you're exiled.
I'd also go with an ogame multiple servers type system... these are parallel worlds, you can travel to another... but it's a one way trip, and will cost you, and you need to convince the ruler NPC to get him onboard (or depose him...)
All of this is going on while other players around you are conquering, banding together and building alliances