Inefficient Python script eating up memory (I believe)
#!/usr/bin/python
# -*- coding: utf-8 -*-

import wx, sqlite3, datetime, threading
from appscript import *


import * is frowned upon as it makes it difficult to trace where names came from.

it = app('iTunes')


I recommend avoiding abbreviated names like it its hard to figure out what it means later.

from AppKit import *



# Create the DB
Tapedeck = sqlite3.connect('Tapedeck.db', check_same_thread = False)
TapedeckQuery = Tapedeck.cursor()
Tapedeck.execute('''CREATE TABLE IF NOT EXISTS plays (id INTEGER PRIMARY KEY, track_id TEXT, track TEXT, artist TEXT, album TEXT, genres TEXT, play_count INTEGER, rating INTEGER, skip_count INTEGER, year_released INTEGER, date_played DATE)''')
Tapedeck.commit()


Generally, performing actions at the module level is frowned upon. You should do it in a main function.

def getSec(s):


Python style guide recommends lowercase_with_underscores for function names. Also, don't needlessly abbreviate.

    l = s.split(':')
    return int(l[0]) * 60 + int(l[1])


I'd have done:

minutes, seconds = s.split(':')
return int(minutes)*60 + int(seconds)


I think its easier to see what's going on    

def addTrack(track_id, track, artist, album, genres, play_count, skip_count, year_released, date_played, rating):
    #print '        --\n        Position: {}\n      Length: {}'.format(it.player_position(),getSec(it.current_track.time()))
    TapedeckQuery.execute('''INSERT INTO plays (track_id, track, artist, album, genres, play_count, skip_count, year_released, date_played, rating) VALUES (?,?,?,?,?,?,?,?,?,?)''',
    (track_id, track, artist, album, genres, play_count, skip_count, year_released, date_played, rating))
    Tapedeck.commit()


loop_int = 1.0
last_track = '0'

def listen():

    global loop_int, last_track


Avoid global variables. You should generally only be using globals as constants. 

    threading.Timer(loop_int, listen).start()


Python isn't Javascript. Instead of playing with threads, use time.Sleep(1) to sleep for a second between each attempt. Put everything in a loop. It'll be easier to follow.

    if it.player_state() == k.playing:
        # check to see if track was restarted
        if it.player_position() &lt; getSec(it.current_track.time())/2 and last_track == it.current_track.persistent_ID():
            self.last_track = '0'


self?

        # has the track played beyond the halfway mark?
        if it.player_position() &gt;= getSec(it.current_track.time())/2 and last_track != it.current_track.persistent_ID():
            today = datetime.datetime.today()
            now = '{}-{}-{} {}:{}:{}'.format(today.year, '%02d' % today.month, '%02d' % today.day, '%02d' % today.hour, '%02d' % today.minute, '%02d' % today.second)


The datetime has a formatting function which may be better suited to that

            print '\nArtist:        {}\nTrack:      {}\nAlbum:      {}\nGenres:     {}\nDatetime:   {}'.format(it.current_track.artist().encode('ascii','ignore'), it.current_track.name().encode('ascii','ignore'), it.current_track.album().encode('ascii','ignore'), it.current_track.genre().encode('ascii','ignore'), now)
            last_track = it.current_track.persistent_ID()
            addTrack(it.current_track.persistent_ID(), it.current_track.name(), it.current_track.artist(), it.current_track.album(), it.current_track.genre(), it.current_track.played_count(), it.current_track.skipped_count(), it.current_track.year(), now, it.current_track.rating())

listen()


As for your actual problem. I don't know this appscript/AppKit you are using. But I'll speculate that under some circumstances iTunes stops responding. Maybe a dialog gets popped or something. As a result, each thread gets stuck waiting for iTunes. But because you set the timer as your first action, a new thread keeps getting started which also gets stuck. Eventually, your poor scripts piles many many threads and that explains the hang. 

If you use the sleep method I suggested above, that should prevent the script from running many threads.