If you've got 2 weeks, you'll be able to hit all the highlights mentioned above, as well as some others, including the Caribbean coast and Lago Izabal. You'll also have time in Guatemala City, which has wonderful museums, restaurants, and nightlife.
Days 1 & 2: Guatemala City
For this itinerary, I recommend booking a hotel in Zona 10, also known as Zona Viva. Once you've set your bags down, spend the afternoon at the side-by-side museums Museo Ixchel del Traje Indígena and Museo Popol Vuh. The first deals almost entirely with the history, manufacturing, and artistry of traditional Guatemalan Maya textiles, while the latter provides a concise yet broad overview of Maya history.
Make dinner reservations at Kacao, and spend the rest of the evening walking around Zona Viva, one of the city's few safe neighborhoods, ducking into any bar or nightclub that strikes your fancy.
Begin Day 2 in Guatemala City's colonial center, or Zona 1. Start at Plaza Mayor, referred to by some locals as "the center of all Guatemala," and make your way to the Catedral Metropolitana and the Palacio Nacional. Take a break on a bench in one of the open-air plazas, and do some people-watching.
For dinner, reserve a table at Tamarindos, my favorite restaurant in the city. After dinner, you'll want to explore the cafes, pubs, bars, and discos in Cuatro Grados Norte, a hip section of Zona 4.
Day 3: Lake Atitlán
Since this is a relatively tight itinerary, I recommend you stay in or around Panajachel. Spend the day walking around town, and be sure to visit the Museo Lacustre Atitlán. For a good hike through some beautiful foliage, head to the Reserva Natural Atitlán. Splurge for dinner with a meal at Hotel Atitlán.
Day 4: Around the Lake
Set aside the whole day to visit some of the other cities and towns around Lake Atitlán. Sign up for an organized tour, or head down to the docks and climb aboard one of the public boat taxis. You won't have time to visit the more than half-dozen towns and villages around the lake, but you must visit Santiago de Atitlán. After that, and as time allows, I recommend Santa Catarina Palopó and San Pedro La Laguna.
Day 5: Chichicastenango
Take a day trip to the market in Chichicastenango. Chichicastenango, or Chichi, is a little more than an hour's drive from Panajachel, and all of the local tour agencies and hotel tour desks in Panajachel can arrange a guided tour or simple transfer. Even if you come here just to shop, be sure to take some time to visit the Iglesia de Santo Tomás and the Museo de las Máscaras Ceremoniales.
You'll get back to Panajachel with plenty of time to enjoy the evening. Head to the Sunset Café for a namesake cocktail, and then head over to El Bistro for dinner. End your evening with a drink at the Circus Bar.
Note: Chichicastenango's market is only open on Thursday and Sunday. Feel free to swap this day of the itinerary with any of the other 2 days around Lake Atitlán to match the market day schedule.
Days 6 & 7: Cobán & Alta Verapaz
On your way to Cobán and the Alta Verapaz, be sure to stop at the Biotopo del Quetzal. Spend a couple hours hiking there and marveling at the richness of the tropical cloud forest. If you're very lucky, you may even spot a resplendent quetzal, the national bird of Guatemala.
Spend the afternoon in the small mountain city of Cobán. Visit the Príncipe Maya Museum, and stop at the Hotel La Posada for a break, some coffee, and a view of the town's main plaza.
Wake up early the next morning, and head for Semuc Champey, a stunning series of pools and waterfalls located about 2 hours out of town. Stop at the small town of Lanquin, but bypass the caves until later in the day. After you're done with Semuc Champey, try the new cave tour at Kan' Ba. If you've still got the energy, head back to the caves at Lanquin around sunset, and watch the amazing spectacle of thousands of bats exiting the cave in search of food.
Days 8 & 9: Lago Izabal
From Cobán, head to Lago Izabal and the rough-and-tumble town of Fronteras. Get a cabin over the water at the Catamaran Island Hotel. In the afternoon, take a boat tour to Castillo de San Felipe, and then go for dinner at the Restaurante Río Bravo, which is also built out over the water. On the following day, take a day tour down the Río Dulce to Livingston. The boat ride in each direction is stunning. In Livingston, you'll want to wander the few streets of this small Garífuna town. For lunch, order a plate of the local specialty, tapado, a seafood soup made with coconut milk. Though time is short, I also recommend hiring a boat in Livingston for a trip to Los Siete Altares, a beautiful series of jungle waterfalls.
Days 10 & 11: Tikal
In my opinion, Tikal is the most impressive ancient Maya city in all of Mesoamerica. You'll probably have to leave Panajachel at an ungodly hour to catch your flight to Tikal, but it'll be worth it. I suggest spending 1 night in the Tikal area, and true Maya buffs will want to stay at one of the hotels right at the archaeological site, which will allow you extra hours to explore. Those with a more passing interest will be better off staying in Flores or at one of the hotels on the lake.
Early international flights from Aurora International Airport in Guatemala City are hard to catch if you're flying from Tikal the same date, so you may have to adjust your itinerary to allow an overnight in either Antigua or Guatemala City before your flight home.
Day 12: Antigua - Getting Acquainted
After arriving at your hotel, spend the rest of the day getting your bearings by starting out at the Plaza Mayor, the center of the city and its principal reference point, and then strolling around Antigua's colonial core.
In the late afternoon, grab a taxi and head to the Cerro de la Cruz, where you'll get a great panoramic view of the city as the sun sets behind the outlying volcanoes.
For dinner, sample some traditional Guatemalan cuisine at La Fonda de la Calle Real, and then stroll around the Plaza Mayor, or head to Reilly's for a nightcap.
Day 13: Walking Around
Take a morning walking tour with Antigua Tours. These tours are highly informative and take you to most of the prime attractions in Antigua. The company has excellent guides, and many of their tours are led by longtime resident and well-known author Elizabeth Bell.
Use the afternoon to hit any of the major sites or attractions you feel you've missed or need more time to fully explore. If you find yourself around the Plaza Mayor and wanting a coffee break, duck into the Café Condesa.
Have a sunset cocktail at the Sky Bar at Café Sky and dinner at Hector's a bustling new bistro.
Day 14: Active Pursuits
It's time to get a little active, so sign up to climb Volcán Pacaya. This is an exciting and energetic climb, but it's also accessible to most people in reasonably good shape. If you do the morning tour, you should be back in Antigua by 1pm.
Save the afternoon to do some shopping. Be sure to visit Casa de Artes, Joyería del Angel, and Textura. If you're looking for bargains, try Nim Po't and the Mercado de Artesanías y Compañía de Jesús.
For your final dinner, pull out all the stops and reserve a table (possibly accompanied by some jazz) at the Mesón Panza Verde. Wind up your last night at Café No Sé, where you'll find a lively mix of locals, expats, and travelers.
Note: This information was accurate when it was published, but can change without notice. Please be sure to confirm all rates and details directly with the companies in question before planning your trip.