"It's the same mass for the same thrust, and the way SE4's repair systemworks, it'd be a disadvantage to use the distributed, multiple-nacelle approach in terms of actual, multiple components (since repair is per-component, not per-kT)."
The only difference- besides repair and number of mouse clicks- is damage. The little engines will loose bits more quickly, but obviously less of a drop than loosing one huge engine. Should be interesting seeing how you handle engine-killers regardless.
Phoenix-D