Guatemala City is organized into 22 numbered zonas, and as a visitor you only need to remember a handful: 10, 14, 4, and 16. Everything you'd reasonably want sits inside that short list, on a plateau at 1,500 meters, with three volcanoes — one of them actively smoking — visible from anywhere with a south-facing window. The rest of the city spreads outward into zonas you won't visit and shouldn't sleep in.
The honest pre-question: should you stay in Guate at all, or push straight to Antigua? Most short-trip travelers do the latter. The case for staying here is the food, the modern infrastructure, the airport-adjacency, and seeing a real Latin American capital before the colonial postcard. Below: the four zonas worth your nights.