Prototypes do nothing on method calls. There is plenty of talk about this in various forums. So they do not affect good users.
If someone tries to call UNIVERSAL::isa(...) with arguments (what use would it be otherwise) they will get the compile time error.
For example, this:
> perl -e 'sub method() { }; main->method(1, 2, 3);'
works, but this:
> perl -e 'sub method() { }; main::method("main", 1, 2, 3);'
Too many arguments for main::method at -e line 1, near "3)"
Execution of -e aborted due to compilation errors.
does not.