Not sure of what your plans are but I would advise that you try an AirBnB either close to your main attraction or along a convenient CTA line. (Blue, Brown, or Red Lines). South Loop is far from everything except the Museums so I would choose something further North. The Loop is dead at nighttime.
River North is probably the best location (bars, nightlife, walkable, part of downtown) but likely the most expensive and hardest to find parking. This time of year, the neighborhoods like Lincoln Park, Wicker Park, Old Town, Lakeview are really nice if you can get a place within 5 minutes walk of a Blue, Brown, or Red line stop. With the CTA you are a ~10-20 minute train ride from downtown.
I second taking the CTA Blue Line from O'Hare into the city. It's about a 30-40 minute ride for $5. $2.25 to go back. Or are you driving in from St Louis?
Give us a more specific list of venues you're planning on going to and we could help select an optimal neighborhood.