1. perl will have a larger startup hit than the C code. If your application doesn't take long to run, that startup time may dwarf the runtime of the entire program. Inline::C will only compound this, at least the first time you run it.
2. does main() do anything? i.e. is there a tight loop where it loads data and passes it to the subroutine? If so, the C code could be faster.
3. is the program runtime bounded by something else, like reading/writing files? If so, the implementation language probably doesn't matter.
4. does the program do something which perl does "naturally" (i.e. internally implemented in highly-tuned C code)? In that case, the perl version may be faster.

c.

You don't need a thought experiment because you can just try it. :)

If the only reason you are using Perl is to provide a main() wrapper, then you are doing extra work that doesn't get you anything. That will be slower. If you want all of your subroutines to be in C, just use C. If your paramount (or only) concern is speed of execution, just use C.

If you think Perl performance might be comparable though, try a Perl prototype and find out empirically. Good luck :)