Ometepe is a large island that can be visited in a day or over a period of weeks. In reference to this map, below is a short summary of some of the highlights and vibes of different parts of the island.
Moyogalpa
Moyogalpa is the port city with a full variety of tourist services and nightlife. Tourists who stay here have faster access to feries, ATMs, economical vehicle rentals, taxis, and more. With a vehicle, visitors can visit main attractions of the island within a day. Also expect high-pressure sales with people hawking their rentals and services upon arrival and while walking the streets. You will feel more like a tourist if you stay here.
San Jose del Sur
The other port town between Moyogalpa and Altagracia, San Jose is a much smaller town with less ferry traffic and thus much quieter than Moyogalpa. Lodging options vary from economical to higher-end options such as Charco Verde and Playa Venecia. Set in an ancient volcanic caldera, Charco Verde has a popular nature reserve along the beach with a lagoon, butterfly garden, and zipline.
Altagracia
The town of altagracia is the central hub for shopping and transportation on the island. All major bus routes go through Altagracia. A more traditional, Nicaraguan town, with cuisine and nightlife catering to locals and national tourists, Altagracia is fun to explore for those wanting a less-hassled, more "authentic" experience. With an archeological museum and an exhibit of pre-Columbian statues in the catholic church grounds, Altagracia is surrounded by pristine beaches, viewpoints, and small towns where you can meet locals and observe daily life. Centro PUMA is located one block north of the central park in town, ready to help thirsty and hungry tourists get oriented and meet the local culture. "Altagracia" also refers to the municipality and southern half of the island, comprising the majority of tourist attractions listed below:
Playa Santo Domingo to Santa Cruz
Enjoying the longest stretch of windswept, sandy beach on the island, the isthmus between Santo Domingo and Santa Cruz is full of tourist options including abundant lodging and restaurants priced from economical to upscale. Nature also abounds with hiking trails and wetland kayak tours near the panoramic beaches. The tourist and farmer's market in Santa Cruz is a fun place for locals and tourists to mingle and share their products and services. Check lake levels before planning your beach time, as rainy season and high water can swallow up all the sandy shoreline--generally February-April is the beach season.
Balgüe and Madroñal
Balgüe is a rural community located at the base of Volcano Maderas with lots of nature and the highest concentration of younger tourists and backpackers. Madroñal is a nearby community that has very similar options and feel to Balgüe, the two towns being a half-hour walk apart. From hostels and jungle-style cabins to an abundance of spiritual, health, and permaculture retreats, both towns offer a diversity of hotels, restaurants, and nightlife to suit adventurous to alternative lifestyles. Nearby Finca Magdalena, with hikes to petroglyphs and viewpoints, is arguably the easiest access to climb the volcano up to its cloud-enshrouded crater lake. Remember, a guide is legally required to summit either volcano on Ometepe.
Merida and San Ramon
These communities located on the west side of Maderas, opposite from Balgue, are quiet and spread out, with less access by public transport. Without any central downtown, lodging in Merdia tends to cater to longer-term tourists and offers full services where everything can be planned and begun starting from your room. Merida is known for its beautiful sunsets, less-windy, leeward beaches, and kayak access to the Rio Istian wetlands on the isthmus. Beach resorts such as Playa Peru and Playa Mangoes are the closest places to kayak to Istian, as well as popular sunset spots. San Ramon, a couple kilometers south of Merida, is famous for its eponymous waterfall. Cascada San Ramon is a short, steep, and rocky hike (4km round trip with 300m elevation gain) with 4x4 access to the upper parking lot, or an even longer, hotter hike from the town far below (more than double the distance and elevation from below). Though beautiful year round, the cascade is more popular in the rainy season because it can dry to a trickle between January and April.