Hokay. St. Louis has its bad neighborhoods and good, just like anyplace does. (Kirkwood has a good side and a bad side, too -- it's a suburb, but the population is over 30K there. However it only has a handful of hotels, all located in the same neighborhood near the intersection of I-44 and Lindbergh Blvd, of these, the Best Western is in the worst area -- in the parking lot of a
WalMart/Lowes/Target/TJMaxx that backs to a relatively rough neighborhood. I shop there at least once a week. You really CANNOT judge safe or unsafe in a suburb of 30K based the actions of two mentally ill individuals.)
Hotel-wise, Downtown is going to be a mixed bag. Generally speaking, the closer you are to the Convention Center, the better the hotel. However, the "name" hotels near Union Station are quite nice: the Omni Majestic, the Hyatt Union Station, the Hampton Inn, the Residence Inn, and even the 2 Drury properties.
The previous poster hit the bad day jackpot with that Days Inn; it is north of the tourist area of the Riverfront by some distance, and is exactly as described. It also advertises rooms by the hour and month, which is always a bad sign in a motel. Generally, in the downtown area you do NOT want to go anywhere north of the Lumiere Place Casino.
All hotels in Clayton are in a good neighborhood that is safe to walk near at night. The Residence Inn in Richmond Heights is the only one kind of iffy at night, but only because it is near a highway and not well-lit.
The hotels in the interstate locations are nicest off of I-44, I-55 and US 64, with the exception of a couple of really cheap ones at I-55@Lindbergh. Other than the major hotels in the airport area, St. Peters or O'Fallon, Missouri, hotels on I-70 are not the best.
The Airport Marriott is perfectly fine in terms of quality, it is the closest hotel to the Main airport terminal, directly on the other side of the interstate highway that runs along parallel to the frontage of the terminal buildings. The only problem that it has is traffic, as it sits right at the dead end opposite the main entrance of the airport, right where everyone has to turn in.
BTW, if you visit Ted Drewes, feel comfortable walking around the neighborhood in the evening. We all do. Francis Park is a block behind Drewes, and on any given evening it is populated by at least 3 dozen joggers, dog walkers, tennis players, and families enjoying the playground. I don't live in the "safe" suburbs; I live in the city itself, in a leafy pre-war neighborhood, and my neighborhood abounds with folks enjoying public spaces on foot, day and night.