There are very few places in the South Loop that are open late enough to be interesting. Of maybe two places in the area that are open till 4am, Miller's Pub is far superior and sure to keep you wanting to stay out late.
They serve food till usually around 2, and I mean actual food, not bar grub. Personally I recommend the crab cakes, but they have a variety of choices. The bartenders are fun, and most of the servers are helpful (though occasionally someone's having a bad night, or just has a not so pleasant attitude). With the Palmer House right next door, expect a lot of business travelers in Miller's, and homeless people waiting right outside the door for your spare change or smoke. Also, business people occasionally drink too much - who knew? So be prepared to witness a fun and entertaining bar fight. But you might want to bring your own popcorn.