There are modifications that change key components of the car (usually engine) and are closer to re-engineering that to modifying.
This list is a place to collect them -- add things you know have been done.
- 6-speed transmission
- Turbo 4 cylinder diesel engine replacement
- Turning down the crank bearings
- Hathaway's Racer
- Replacing the timing chains with BorgWarner Morse Hy-Vo chains
- (as commonly used in GM vehicles)