Can a video game potentially detect arduino leonardo?
Yes.   

First you'll need to define how you plan to inject the new input signal, into the data "packets" as a spoof of controller signals, or just jumping the switches?  

In the context of any modern gaming console, it could be detected. Easily. Consoles and controllers use any number of proprietary protocols which sync.commands to improve response and reduce controller lag. If you're just jumping the switches, then no, you could simulate hadouken and probably get away with it just fine.

If you're referencing PC gaming, then that would be hard if not impossible with the variance of input control available.  The best deterrent would be the security of the game software itself and the genre of the gaming. Some games actively encourage Hotkeys.