Apart from the Tbilisi-Mestia flight, the sleeper train to Zugdidi followed by a marshrutka to Mestia is in my opinion the most comfortable way of travelling to Svaneti. Book train tickets at least a day in advance (seats), or earlier if you want a sleeping compartment. The train leaves Tbilisi around 23:00 and arrives early in Zugdidi around 7:00, where marshrutkas are waiting to take you in 3-4 hours to Mestia (15 GEL). We tried to get onto the flight but the Pegasus airlines office at Tbilisi airport seems to have irregular office hours and were closed when we got there. We also heard that it was fully booked for two weeks in August, but for September it might be okay. Note that the flight is cancelled sometimes when the weather in Mestia is bad.
Considering accommodation, I can really recommend the Grand Hotel Ushba in the Becho valley (but more expensive than homestays), Rosa's Guesthouse in Mestia (Rosa can help you arrange transport and is just a wonderful and helpful lady serving delicious breakfasts) and Riho Guesthouse in Ushguli (wonderful location, great food, great people and comfortable beds). It seems like most people just do a daytrip to Ushguli but I would definitely recommend staying there for one or two nights, it's a wonderful place after all day-trippers are gone.
We did nearly all of the hikes possible in the Svaneti region - there are good descriptions on the website of Svaneti Trekking: http://www.svanetitrekking.ge/eng/index.htm, and everything is perfectly waymarked. There are even signposts in latin script to point you into the right direction. Really no need to take a guide. Possible multi-day hikes would be the trek from Mazeri in the Becho valley to Mestia via the Guli pass (camping on the pass), or the popular three-day Zhabeshi - Ushguli trek (homestays in Adishi and Iprali). You do need to cross a river on the second day after Adishi and in case of heavy rainfall, you might need to arrange a horse in Adishi to cross it.
Other highly recommended hikes: Ushba glacier from the Becho valley, Koruldi lakes and Tsvirmi village from Mestia and the Shkhara glacier from Ushguli. Remarkably, no maps are sold in Svaneti so it's best to get them from the Geoland in Tbilisi if needed. However, we just used our GPS, the route descriptions and the waymarking and never got lost.
Enjoy Svaneti!