You'll find 3 excellent choices right in the South Boston Waterfront neighborhood, as well as several others very close by.
Any of these Boston hotels will be a fine choice. Here's an overview of what each offers so that you can choose the best one for your visit.

The Boston Westin Waterfront, 425 Summer Street, connects directly to the Boston Convention and Exposition Center (BCEC) through a sky tunnel. If you're attending an event at the BCEC, the Westin will be your most convenient choice.
A Silver Line transit stop in front of the BCEC gives you easy access (5 minutes or less) to Boston's South Station and Downtown Boston. Alternately, you can easily walk there (8-10 minutes).
Like the other two South Boston Waterfront hotels, the Westin (part of the Starwood hotel group) offers a variety of food and beverage options, a nice swimming pool, and all the amenities you'd expect in a comfortable business hotel.
And like the others, the Westin is not actually on the waterfront. However, with the water only 3-4 blocks away, it's a short walk.

Seaport Hotel (1 Seaport Lane and Northern Ave, almost directly across from Fish Pier) connects to the Seaport World Trade Center, and will be your most convenient choice if you're attending an event here.
The Seaport (and the Renaissance, just a block up the street) are also the most convenient hotels if you plan to take a water taxi from Logan Airport to the South Boston Waterfront. A water taxi stand is directly across the street from the Seaport.
The independently-owned Seaport Hotel offers similar amenities as the other South Boston Waterfront hotels, with one addition: you can bring your small-to-mid-sized dog to this pet-friendly hotel.
Another nice plus is Aura, the hotel's full-service restaurant. With a creative chef at the helm, it's an appealing dining destination whether or not you're staying in the hotel.

Renaissance Waterfront Hotel (606 Congress Street) is slightly closer to Downtown Boston than either of the other two South Boston Waterfront Hotels. You'll find the same mix of high-end business hotel amenities here, which means that you'll have a very comfortable stay. The Renaissance is part of the Marriott hotel group.
Like the Seaport Hotel, the Renaissance is only a block or two (depending on how you count) from the BCEC, as well as being close to all the other neighborhood attractions. It's especially convenient to the Institute of Contemporary Art (ICA), just across Northern Ave.
With 3 excellent but fairly similar hotels to choose from in this neighborhood, how do you pick one?
Here are my suggestions:
What if none of these factors apply?
Make reservations in whichever hotel offers the cheapest rate.
You'll be happy in any of them.
With only 3 hotels located in the South Boston Waterfront, and lots of conventions and other activities in this neighborhood creating demand for hotel accommodations, you may try to book a room only to find that they're all full.
Fortunately, several other excellent choices are close by.
The Intercontinental Hotel Boston (510 Atlantic Avenue), located on the Downtown Waterfront just north of the Moakley Footbridge, offers lovely views, impeccable service, and luxury accommodations.
Possibly even more luxurious and just a bit farther north, Boston Harbor Hotel also boasts sweeping waterfront views. In the summer, their Summer in the City series features jazz concerts from their Blues Barge, Movies by Moonlight, and more. During late winter and spring, their internationally renowned Boston Wine Festival draws guests from all over the world. Their spa is amazing any time of the year.
Although not on the water, the Langham Hotel (250 Franklin Street, in Boston's Financial District) is another luxury option where you can sometimes find surprisingly affordable rates, especially on the weekends. Their Chocolate Bar, in Cafe Fleuri, is a popular destination. The Langham also boasts one of the best spas in the city for the ultimate in pampering and rejuvenation.