We found the area to be quite busy with shops and eating places. The travelodge is directly across from Marylebone station which is no problem at all. The noise at night with traffic could be a problem if you are a light sleeper. We have stayed here at least three times and usually no problems, the last time though was very noisy with lots of people standing outside the sports bar across the road -the noise seemed to reverberate all around. Just to point out though that we have never had that before and we assumed it was because it was the night Mo Farrah was running in the Olympics.
As far as safety goes we have never had a problem but then we don't really stay out late at night I would say just take the usual precautions as you would in any strange area. If you are wanting to stay out late and travel back to this travelodge the bus stops around the corner and you also have the underground right across so shouldn't be any issues.