I think it's better to keep the speeds the same and handwave the physics to avoid fights being all 1 shot kills.
Actually, I don't think that's necessary. True, when having great differences in speed, the railgun hits will probably be one hit kills. But that's it, "one hit kills". If it doesn't hit you, it doesn't kill you. The "time to displace ship once" (tds) is probably quite important here. That means the time needed to accelerate in such a way, that the ship has not a single meter at the position it would be when not having accelerated. For example, for the geosurvey ship in the test campaign this would be about 19 seconds. But let's take the warship on page 4 of the newtonian fighter thread. It has a neat 22. 5 second tds. That means when accelerating constantly and randomly, even when closing in at let's say 40,000km/s (quite a high figure), that still means that, even when your gun is hitting perfect in the center of a target at no matter what range, you'll still have an 100%-hit range of only 900,000km. Therefore the game will probably be about probability. Shoot enough, and you're bound to hit at least something.
In fact, I think I can more or less see how combat will turn out:
Long Range:
about 50mkm and more:
Missiles rule the vacuum. They can correct for course changes of the enemies, and they can accelerate to high speeds. Two alternatives exist for their armament: Kinetic (including probably shrapnel) and nuclear (including beams).
Kinetic warheads will have the advantage of depending on the speed difference. A 1ton warhead hitting you with 10m/s will probably just ruin your paint job, but the same warhead crashing into you at 4,000km/s as you try to reach the enemy will pretty much ruin your day, a. k. a. pulverizing the ship (although the jury's still out on how much exactly you're screwed). Their disadvantage? They depend on the speed difference.
Nuclear warheads on the other hand always deal the same damage, independent of movement. And laser warheads will make point defence more difficult. More to that, later.
Mid Range:
Long live the railguns! And someday lasers. This is where the aforementioned spraying will occur. Here, again, the same rules apply as above: Railguns are great when you and the enemy are flying head-on. When however you're on a parallel course, they will not do much damage. And if he's flying away? Forget it.
Lasers on the other hand (when implemented as I'm thinking they will) will hit with always the same damage, no matter who's moving where. And should have a higher effective range than railguns. That cruiser I mentioned above? You have a range against that of about 22. 5 lightseconds, not considering jitter and such. That are 6. 75mkm!
Point Defence:
Now it's getting interesting. What is stopping these kinetic missiles to fly through your ship? In short, you of course ;-). There have been different ideas to deal with those missiles:
Dust: Simply use their speed against them, by shooting dust (or small spheres or whatever) in the path of enemy missiles, they will use their kinetic energy to kill them. Is of course dependent on different factors, all of which are discussed at Impact Physics.
Nuclear Antimissiles:
Shoot one, kill dozens. In theory. Has, of course, to be shot quite some time before the enemies missiles reach you, or you will destroy that armor yourself. And, the enemy could send nuclear antinuclear anti missiles with theirs.
Missiles with shrapnel: Basically the dust above, but at a range.
And my favourite, although not yet implemented: Lasers. Why? Because they should be able to kill missiles at quite a big range. Using the nuclear anti-ship missile as an example, estimating their length to about 4 metres, one can see that a laser without jitter should be able to hit it at 100% certainty at a distance of 25kkm. While, without knowing the strength of lasers one cannot certainly say that this will one-hit-kill such a missile, even trading the warhead for armor it would need less than 800MJ at ceramic composite armor to at least punch a hole through. Looking at the railguns that seems possible.
And even if there is debris, at 25kkm even a slight deviation will carry it far, far away from the attacked ship.