1) Often I see a large number of missiles, enough to blast all my ships, in an unstoppable advance towards my fleet, only to have them magically disappear as combat ends due to all enemies dying to my missiles. I find this 'unrealistic' and would rather see combat end only once all missiles have hit their targets or have been otherwise destroyed.
2) Currently, all the defenses against missiles need to scale linearly with the amount of enemy missiles - i.e. if the enemy sends 4 nuclear missile, suppose I think I need ~ 10 pd lasers to shoot them all down, then for 40 missiles, I'd need ~ 100 pd lasers. I'd rather see some counter that scales better, like for example an area-effect weapon that destroys half the missiles in a certain area - no matter if there are 4 or 40. This would make the simplest direct mass-missile strategy ineffective eventually, as well as making positioning in combat matter a bit more. (sending missiles from different directions makes them all harder to intercept. When several volleys pass through the same tiles, targeting them with the aoe is particularly effective.) This will also turn an entire fleet targeting a single ship with missiles turn from a death sentence to that ship to an easily counterable move.
3) I know this has been talked about, still, in my opinion missiles are too fast compared to ship movement. For example enemy moves forward and launches missiles, my ship turns around and runs as far as possible, and still gets blasted in the very first turn (while moving!). This will not change if you reduce (missile damage)/(ship HP) ratio, as if the enemy has enough missiles, this will keep happening. Missiles hitting you on your own turn severely limit maneuverability, and makes me feel like I have no freedom to change anything about the way the battle goes.
In my opinion it would be best if missiles only moved during the firing party's turn, this way you would lose the very artificial ability to manipulate the missiles position relative to intercepting ships, you would be free to move your ship anywhere you wanted, and missiles would still hit as they'd still be much faster than ships.