Back when Cervelo was doing 48-hour test-rides, I took an S2 home and compared it back-to-back with my Cervelo RS. The aerodynamics are definitely impressive. Cruising at high (18+mph) speeds seemed to be effortless. In the end, I returned the bike after less than 24 hours, though.

My biggest complaint was the aerodynamic seat post. Unlike the rest of the bike, the seat post was insanely stiff. On poor-quality roads, like the ones I normally ride, the S2 felt like you were riding a jackhammer not an expensive carbon fiber frame. I also wasn't terribly impressed with the climbing ability. On my first hill, I literally stopped twice to make sure the brakes weren't dragging on the rims! Of course, at that time Cervelo was selling the complete S2 bikes with relatively heavy/cheap Shimano RS10 or RS20 wheels.

Personally, I'd go with the R3. I would expect the ride to be every bit as comfortable as my RS, with a slightly more aggressive riding position and slightly quicker handling. If you want better aerodynamics, you can always invest in some deep cross-section carbon fiber wheels...