although my top 10 is very close... i always feel that The Thrill Is Gone is my #1 song. I can listen to that in any mood or situation. Particularly the version by Gary Moore live with B.B. King.
A lot of today's music has a good melody but lacks in lyrics. I feel it's rare to find a song that has both decent melody and lyrics. My favorite song is an example, Last Summer by Lostprophets.