Verifying user accounts on SMTP servers
What you really want is a robust argument parsing. This calls for argparse:

import argparse
import os.path

def is_file(f):
    if os.path.isfile(f):
        return f
    raise OSError("{} does not exist".format(f))

parser = argparse.ArgumentParser(description="SMTP user checker")
parser.add_argument('server', help="IP address of server")
parser.add_argument('usernames', type=is_file, help="Path to list of user names")
parser.add_argument('--port', '-p', type=int, default=25, help="SMTP port of server")
args = parser.parse_args()

smtp_conn = create_connection(args.server, args.port)
print smtp_conn.recv(1024)


Note that it is already standard practice of Python to print any error and exit afterwards.

Additionally, you probably want to close your SMTP connection even in the case of an exception. For this, you could use a contextmanager:

from contextlib import contextmanager


@contextmanager
def create_connection(host, port):
    try:
        sock = socket.socket(socket.AF_INET, socket.SOCK_STREAM)
        sock.connect((host, port))
        yield sock
    except socket.error:
        # Handle specific exception here, or not and re-raise
        raise
    finally:
        # Ensure sock is closed under all circumstances
        try:
            sock.close()
        except UnboundLocalError:
            # Did not even succeed in creating the variable, nothing left to do
            pass


And then use it like this:

with create_connection(args.server, args.port) as smtp_conn:
    print smtp_conn.recv(1024)
    with open(args.usernames) as users:
        for user in users:
            print smtp_verify(user.strip(), smtp_conn)


Note that Python uses read mode by default when opening a file, so there is no need to use 'r'.

Final code:

import argparse
import socket
import os.path
from contextlib import contextmanager


@contextmanager
def create_connection(host, port):
    try:
        sock = socket.socket(socket.AF_INET, socket.SOCK_STREAM)
        sock.connect((host, port))
        yield sock
    except socket.error:
        # Handle specific exception here, or not and re-raise
        raise
    finally:
        # Ensure sock is closed under all circumstances
        try:
            sock.close()
        except UnboundLocalError:
            # Did not even succeed in creating the variable, nothing left to do
            pass


def smtp_verify(username, smtp_conn):
    smtp_conn.send('VRFY {}\r\n'.format(username))
    return smtp_conn.recv(1024)


def is_file(f):
    if os.path.isfile(f):
        return f
    raise OSError("{} does not exist".format(f))


def parse_args():
    parser = argparse.ArgumentParser(description="SMTP user checker")
    parser.add_argument('server', help="IP address of server")
    parser.add_argument('usernames', type=is_file, help="Path to list of user names")
    parser.add_argument('--port', '-p', type=int, default=25, help="SMTP port of server")
    return parser.parse_args()


if __name__ == "__main__":
    args = parse_args()
    with create_connection(args.server, args.port) as smtp_conn:
        print smtp_conn.recv(1024)
        with open(args.usernames) as users:
            for user in users:
                print smtp_verify(user.strip(), smtp_conn)


Alternatively, you could use the docopt module for this:

"""SMTP user checker.
Usage:
  argparser_comp.py SERVER USERNAMES [(-p &lt;p&gt;| --port=&lt;p&gt;)]
  argparser_comp.py (-h | --help)
Options:
  -h --help          Show this screen.
  -p &lt;p&gt; --port=&lt;p&gt;  SMTP port of server [default: 25].
"""

import socket
import os.path
from contextlib import contextmanager
from docopt import docopt


def is_file(f):
    if os.path.isfile(f):
        return f
    raise OSError("{} does not exist".format(f))


def parse_args():
    args = docopt(__doc__)
    return args["SERVER"], is_file(args["USERNAMES"]), int(args["--port"])


@contextmanager
def create_connection(host, port):
    try:
        sock = socket.socket(socket.AF_INET, socket.SOCK_STREAM)
        sock.connect((host, port))
        yield sock
    except socket.error:
        # Handle specific exception here, or not and re-raise
        raise
    finally:
        # Ensure sock is closed under all circumstances
        try:
            sock.close()
        except UnboundLocalError:
            # Did not even succeed in creating the variable, nothing left to do
            pass


def smtp_verify(username, smtp_conn):
    smtp_conn.send('VRFY {}\r\n'.format(username))
    return smtp_conn.recv(1024)


if __name__ == "__main__":
    server, usernames, port = parse_args()
    with create_connection(server, port) as smtp_conn:
        print smtp_conn.recv(1024)
        with open(usernames) as users:
            for user in users:
                print smtp_verify(user.strip(), smtp_conn)