The point of #! is to instruct the system which intepreter to start for the script contained below it. If you've already started an interpreter (via calling perl on the command line), the #! is just a comment.

Perl is courteous, though, so even when it's not being called via #!, the interpreter will check the command-line options on that line and attempt to respect them. For example, using #!/usr/bin/perl -w will turn warnings on even when you launch your script like perl script.pl.

Shell expansion isn't done on the shebang line by design: the spec for that mechanism demands a real path for various reasons.