I can't help much with Quetzaltenango (usually referred to as Xela) because it's been years since I've been there - I'm not much of a city person and it's the 2nd largest city in Guatemala. I haven't spent much time in Guatemala City in recent years, either. If you planning to spend some time there exploring, you'd probably want to stay in Zone 1 or 2. If you're planning to just shuttle from the airport and take a bus the next day, you could stay near the airport; a good hotel could set you up with a driver to take you around to the main historic sites and museums if you want.

Here's a link to my favorite hotel in Guatemala City, just minutes from the airport, breakfast and airport shuttles included.
www.hostelvillatoscana.com

Check out the reviews on Trip Advisor where you can also look up hotels with good reputations in other parts of the city:
http://www.tripadvisor.com/ShowUserReviews-g292006-d675319-r147704202-Hostal_Villa_Toscana-Guatemala_City_Guatemala_Department.html

Re: buses, you could taxi to the bus station and take a pullman from there or hire a shuttle to pick you up. Here are 2 agencies I've used really successfully for transportation in Guatemala:
www.adrenalinatours.com
www.rainbowtravelcenter.com

My photos with blog and travelogue links on the main page of each collection are below in case you're interested - all my recommendations are embedded there. Happy trails!
http://www.flickr.com/photos/staceyholeman/collections

Just got back from Guatemala. Most of my time was in Panajachel but some in Guatemala City and a night in Xela. Here are my suggestions.

In Guatemala City I highly recommend Hotel Spring (http://www.hotelspring.com). Reasonable rates (they have shared bath, private bath and "new" private bath choices) and in a very convenient location. Two blocks walk to 6th Ave (the pedestrian mall) and lots of other stuff.

There are no safe buses that run to the airport. Expect to pay about Q100 for a cab from the airport to Zona 1/Hotel Sprint.

The buses are fine and a lot more interesting than a "Gringo shuttle". It is Q30 (less than $4) from Guate to Panajachel. I have been on the Xela to Guate bus (returning to Pana) but not paid the full fare but would guess it is about Q40.

As for Xela, a friend runs the Xelapages web site. Here are his suggestions to me:

Here is a list of hotels in Xela that you might want to consider when you bring your friends this month. Most of these are in Zona 1 the center of Xela.

http://www.xelapages.com/hotel.htm

There are also a dozen or so guest houses around town.

http://www.blackcathostels.net/eng/xela/index.html

http://7orejas.com - nice place about 2 blocks from my Internet shop.

If you need to get around in Guatemala City, see http://a42.com/site/pg/s/1/3/63/73/346/406 for information on Transmetro. Cheap and safe.

Six months ago Guatemala was not really on my list of "good places". I have been very impressed with it. While I don't really like cities, Guatemala City is clean, organized and improving every day. Panajachel/Lake Atitlan is amazing. Have a good trip.

In Guatemala city we are staying at the Barcelo, formally the Marriot which is in Zona 9. Close to museums, emabassy and the airport. Look at tripadvisor.com for places you are traveling to. There should be some lovely ones in the areas you are going to visit. Also check into www.transportguatemala.com for transport options. A shuttle bus may be easier for you than the local bus which can be a great experiance but also and adventure which may not be your objective at this point. Good luck.