Now that PEP-552 is accepted, we'll need an actual implementation. Besides the core import changes, there are some perquisites improvements. For one, our SipHash implementation needs to be changed to accept an arbitrary key. Also, the PEP also introduces the first "long" option to the interpreter, so the getopt implementation will have to be enhanced.
Increase the size of the constant part of the signature. Currently it is only 2 bytes (3rd and 4th bytes are b'\r\n') and it is hard to use them in tools like file.
Split the magic number on two parts. The first part encodes backward-incompatible changes and can be updated only in new feature releases. The second part encodes backward compatible changes and can be changed in bugfix releases.
Maybe even include the minimal Python version? This would simplify the launcher which needs to map a magic number to Python version.