I would suggest being able to move the engine around on the chassis and the choices affecting the weight balance & handling. Also Inline engines could be mounted in a slant which would take more width, but it would allow the front body of the car to be lower and more aerodynamic.
The transmission could also be moved around, albeit in a much more limited space.(depending on the size of the car but it would either be in the normal place or infront of the rear axel)
The type of engine should also be a factor. For example using a Flat engine would mean a lower centre of gravity, and also if mounted in the front would allow a more aerodynamic car.
For example the early porsche 911's had problems with too much oversteer because of the rear mounted engine. However the position allowed more cargo/passenger space than in a mid engined car. While most companies stopped using the RR congifuration, they stuck with it and they improved the suspension and eventually switched to AWD which fixed alot of the handling issues...
Other things like cramming an engine into a small space should make for higher maintenance costs. For example the 300ZX's V6 is crammed soo tight under the hood its a pain todo even alot of basic maintenance. Another example is one of the 90's Ford Taurus SHO with its transverse mounted V8 it was very hard to change the sparkplugs closest to the firewall.
These kind of little choices can make a big difference in the design of a car. There are soo many advantages and disadvantages to each engine type and where its mounted and the more of these types of things can be simulated in the game it will make for a very deep and fun game.