Lithuania offers multiple locations for a great weekend trip. All of the following should give enjoyable 2-4 days, but, of course, one may also decide to spend a relaxing week there, or to just check the highlights in a single day. The ranking is based both on the number of interesting localities and the easiness to get there and explore the location in a weekend.
1.Vilnius is both Lithuania's capital and top destination. Once a capital of Europe's largest Medieval state it still boasts a massive Old Town full of Baroque church spires (one church for every 700 locals). It is joined by Lithuania's best entertainment and nightlife as well as sobering sights reminding of the 20th-century genocides and the collapse of Soviet Union (which started in Vilnius). As a location of largest airport Vilnius is also easiest to arrange a weekend trip to.
2.Kaunas is the Lithuania's second city. Having served as a "temporary capital" in 1920-1940, Kaunas excels in the architectural heritage from the interwar period (art deco and Bauhaus). Some of the key national museums are still located in Kaunas. Furthermore, Kaunas has an authentic Medieval old town that once used to be frequented by Hanseatic merchants. The downtown is still entirely surrounded by 19th-century Russian military fortifications that were meant (yet failed) to stop a German invasion. Kaunas airport offers numerous low-cost flights to Western Europe or alternatively one may arrive at Vilnius airport (~100 km away).
3.Neringa (Curonian Spit) is the top natural attraction of Lithuania. A 99 km long narrow peninsula (50 km of the length within Lithuania) is one large National Park, full of windswept sand dunes ("Lithuanian Sahara"), pristine pine forests and fishermen villages that now double up as rather exclusive resorts. Arrival is possible via Palanga airport 30 km away or by ship to Klaipėda port (albeit passenger routes are limited at both).
4.Klaipėda, Lithuania's 3rd largest city, had its Old Town ravaged by Soviets who destroyed its churches. Still, Klaipėda unique feel of the seaside and German history (the city was under German rule until World War 1 and known as Memel). National Romantic (heimatstil) and timber-framed houses, as well as 19th century and World War 2 German fortifications, are interesting to watch, joined by seaside entertainment (dolphinarium, sea museum, beaches) as well as a lively Old Town. Best to arrive at Palanga airport 30 km away or Klaipėda port.
5.Palanga is the Lithuania's top seaside resort. Come for a summer weekend (especially in July/August) to see it crowded to the maximum. Join the masses flocking to its wide sandy beaches and Basanavičiaus street, the main space for every-evening outdoor gigs, funfairs, and other entertainment. If one prefers more sightseeing, there is a large 19th-century palace (now hosting Amber museum) and wooden villas. One drawback is that hotels may get fully booked if the weekend is hot, so order in advance. Best to arrive to Palanga airport.
6.Druskininkai is the Lithuania's top spa (mineral spring) resort. It has recently expanded and went more upscale as the old spas were joined by modern entertainment such as an indoor water theme park (with sauna space), an adventure park and an indoor Alpine skiing track. Add saunas, spas and calm streets with cute wooden villas to that and you'll have more than enough to do for an active (or relaxing) weekend. Best to arrive at Vilnius airport (~140 km away), unless you are from Belarus or Poland in which case you may drive.
7.Dzūkija National Park is the Lithuania's largest forest. Opportunities there include kayaking as well as traditional free-to-everybody berry-picking and mushroom-picking (or buying fresh berries and mushrooms from locals if you are unsure in your ability to distinguish edible from inedible). There are numerous traditional wooden villages deep in the forest where seemingly little has changed for some 100 years. While the forested nature itself is the main draw, some of the forest towns and villages offer pretty sights, such as Liškiava monastery. Best to arrive at Vilnius airport (~130 km away) and hire a car.
8.Šiauliai is the most famous for its Hill of Crosses, where millions of these Christian symbols have been brought in in defiance of the Soviet atheist regime. Now visited by religious and non-religious alike this inspiring place gives many possibilities for contemplation, prayer, meditation or simply being in awe of its beauty (Lithuanian wooden crosses are a UNESCO-inscribed art. While Šiauliai city itself is unappealing after it has been ravaged by World Wars, it offers numerous museums to spend the rest of the weekend. Best to arrive at Riga airport (120 km away), which is the largest airport in the Baltics (there is no customs control on Lithuania-Latvia boundary and Hill of Crosses is en-route from Riga).
9.Samogitia National Park is famous for its Plokštinė Soviet Nuclear Missile launch site, where an authentic launch shaft may be entered and Cold War museum explored. The rest of weekend may be spent checking wooden churches, enjoying various lakes or going to the Orvidai farmstead - a mystical artwork to some, a junkyard to some others. Best to arrive at Riga airport (~180 km away) or a far less popular Palanga airport (~50 km away) and hire a car.
10.Lakes of Aukštaitija are dotted around a massive area that also has authentic old villages, lakeside towns, old wooden churches (e.g. Palūšė) and strange sights such as a pagan shrine, a UFO-like museum-cum-artwork, and a Soviet nuclear town. However, one needs a car and much driving to explore it all in a few days; alternatively, one may hire a bike to ride just around the national park. Arrival to Vilnius airport is the most logical.