I have a Sky Redline and have driven both modified and unmodified S2000's ad there is no comparison. Other than the fact they are two seated roadsters they shouldn't even be considered against each other. It's kind of like an Elise and a Corvette actually, similar price range, both excel at different things but once someone drives both, they know which one is their car.
The S2000 is very light, very small, rev happy, and the wind buffeting and road noise is loud with the top down or up. With the top down there is little chance in having a conversation or listening to music. The steering has a much nicer feel and the transmission is like heaven in your hand. As a corner carver, very few cars can match it.
The Sky Redlike is bigger, it has more insulation, and the ecotec LNF is one hell of a motor. The torque is unbelievable for a 4 cylinder stock and with a <$500 tune it will blow your mind. The top is well insulated and the car is very quiet compared to the S2k. The transmission was pulled straight out of a truck and is a bit clunky, though I like the clutch engagement after getting used to it. Steering feel isn't even in the same class as the S2k, and the steering wheel is too large. The interior is far more comfortable, the sound system is far superior, and I think it looks better as well. The top isn't as hard as the reviews make it out to be IMO.
So S2K is more striipped down "drivers" car. Sky RL has some niceties and makes up for the weight disadvantage with a lot of extra power. Stock, in a 1/4 mile, the sky will barely outpace the S2k with both running around 14 seconds. With a tune the Sky drops into the very low 13's and high 12's.
I chose the sky because I am more about passing power, highway cruising, and evenings at the drag strip than anything else and I have done a few long distance trips in it as well. Despite the fact the S2k "feels" better on the track the Sky usually puts down better numbers.
Either way you really can't go wrong, they are both highly enjoyable. In all honest though, if I were buying all over again, I'd pick up a 370z.