Guatemala City isn't much to write home about, but it's the main travel hub that connect you to all corners of the country. It's easier and safer to organize a shuttle to pick you up at the airport. GuateGo is a handy resource that lists several shuttle companies based on route.
Antigua: Only 50 mins from Guatemala City, Antigua is popular for a reason. It's bursting with culture and lively nightlife. For hikers, you couldn't be in a better spot, you'll have the chance to do an over-night hike up Volcano Acatenago, camp on the summit and watch its neighbor, Fuego erupt in all of its glory.
If you aren't a hardcore trekker, go for Volcan Pacaya, it's an easier hike with the option to go on horseback. You'll get to roast s'mores in the lava!
Lake Atitlan: Formed out of a massive volcano crater, Lake Atitlan actually sits on top of a sunken city and can be reached by a 2.5hr shuttle (and a bumpy tuk-tuk down a mountain). Surrounded by 3 brooding volcanoes, a cluster of 11 eclectic towns dot its shores, accessed by boat taxi.
Many travelers come to this area to learn Spanish at a homestay, and I'd strongly recommend doing the same. This immersive experience allows for a more profound understanding of daily life, customs and cultural richness of indigenous families.
Across the water, San Marcos la Laguna and San Pedro are both weird and whimsical hangouts for Bohemian types. I spent almost 6 months here volunteering and although the town comes highly recommended by most backpackers, if you're looking to find an authentic Mayan village, sadly this isn't it. Instead, I'd recommend Santa Cruz or Jaibalito.
San Juan, a quiet village on the lake, shouldn't be skipped either. It's known for its women's weaving co-operatives that specialize in naturally dyed textiles that align with the Mayan moon calendar.
These cooperatives play a pivotal role in the community, preserving traditional weaving techniques and enhancing the economic conditions and overall quality of life for the local women. It's also the unofficial gateway to the sunrise Indian Nose Hike, remember to go with a guide, though!
Tip: It's important never to drink the water here (not even to brush your teeth) and wash any fruit/veg before cooking to avoid parasites from the lake.