While acceptably safe by day, central Comayagüela is no place to be hanging out at night. But if your bus arrives late and you have an early bus connection the next morning, you might as well avoid trekking over to the other side of the river for your accommodations.
The 
Hotel Condesa Inn (12 Calle and 7 Av., tel. 504/237-7857, US$15 s, US$18.50 d) is a good choice, nearby several bus companies, with clean, pleasant rooms. A restaurant and laundry service are on-site.
A few blocks away, the four-story Hotel San Pedro (tel. 504/222-8987, US$5 s/d communal bath, US$9 s/d private bath), on 6 Avenida between 8 and 9 Calles, is as basic as it gets, but popular for its ultra-cheap, clean rooms.
Just across the street, the Hotel Plaza Real (tel. 504/237-0084, US$10.50 s, US$13 d, about US$4 more for private bath) is a step up, with 27 rooms around a leafy courtyard and free coffee served all day long.
Along the lines of the Condesa (but not quite as nice), is the Hotel Centenario (tel. 504/222-1050, US$18 s, US$37 d) on 6 Avenida between 9 and 10 Calles. All rooms have TV and telephone, and well-worn sheets and mattresses.