As been stated, all depends on what you want it for and budget.
For a modest budget , if you're talking about lap times, then as Dunsy says, brakes/tyres best mod. Or strip it and get it corner balanced, will make drastic improvement to handling acceleration and braking.
With all Hondas I/H/E mods are all important but none of these on own are going to give much of an increase.
If you're talking power, as Kozy says displacement, plenty of B18 swaps on here. And if you count dropping a K20A in as 'one mod', not a bad choise.
Alternatively is forced induction, but you can't really count a supercharger/turbo set up as a single mod.
Personally I think for straight line speed the most cost effective mod would be a NOS setup, though not many people on here seem to run it.
Another alternative would be a remap, someone on here recently got some really good gains on what was effectively a stock motor, with a fair gain in mid range torque which would improve flexibilty and all round driveability.
My final 'mod' would be yourself. About a year ago I did an advance driver track day kind of thing with some ex police drivers, I think this improved my b road 'lap times' more than many individual mods would have.