Otherwise, Mariners are out of town. You could get a nice seafood dinner: Elliott's down on the waterfront; Salty's at Alki has a great view into downtown. There are plenty of nice places depending on how much $$$ you want to spend.
What hotel will you be in?
Taking a ferry ride across to Bainbridge and back is always cool.
Maybe go up to Queen Anne, find Kerry Park on Highland Ave and take the postcard picture.
Wander through Pioneer Square (before dark). Hit Elliott's Bookstore for some good local books.
For just one night I'd stay somewhat close to / in downtown.
I just got back from my first visit to Seattle. It was a blast.
The Experience Music Project museum is very cool. It's open until 8 each night during the summer. Worth a visit. It's in the Seattle Center near the Space Needle. You can take a monorail there from one of the downtown malls (Westlake?)
We had a great seafood dinner at the Flying Fish, which is in a cool neighborhood called Belltown.
You could check out Fremont, which is a very hip, trendy neighborhood. That's what I expected from Seattle. Downtown is very cosmopolitan, but Freemont and Wallingford are funky.
I didn't really have a choice on hotels. I'm at the Doubletree at the Seattle airport. Thanks for the suggestions. I will have a car but if there's other good transportation from the airport area that would be preferred, I think.
I think I'd be interested in doing something down by the waterfront.
There are ferries that take you to different islands in Puget Sound. I took a ferry to Bainbridge on a Saturday afternoon (you catch it at Pier 52). It was nice to get out on the water, but I wouldn't do that if I only had one night out there. It's a good weekend time kill, but not worth it given your time constraints.
Capital Hill is cool. There's one of those urban bowling alleys/bars there called The Garage, I think. Very cool place.
If you want a pretty cool view of downtown, the waterfront, Fremont, etc...
take the 99 north just south of downtown. You will get a very cool perspective of downtown and the Puget Sound. Continue on 99 and you'll pass relatively close to the Space Needle and into Fremont area. Can't recall the exact route, but you'll exit and continue near the waterfront and end up at Ray's Boatyard for sunset and a solid dinner.
Its called Ray's Boathouse. Best Happy Hour in the city. Gotta sit in the upstairs bar and get the calamari, clams, mussels and ahi tuna. Watch boats come and go through the locks. Do a google search for Ray's Boathouse Ballard
Happy hour is from 4-6pm, get there at 4 and snag a window table.
During my interview weekend in Seattle (I live here now.), I asked a local to recommend a restaurant. He recommended Etta's, a Tom Douglas restaurant. It is one of my favorite restaurants. It is near Pike Place market, so you can walk around downtown after you are done eating.
Have fun. Hopefully you can come back for more than just one night. The Link
As Natron stated Ray's Boathouse is awesome for happy hour and hanging out; Jive Turkey's rec. for The Flying Fish in Belltown is also a good choice. I've been here 6 1/2 months and have yet to go to EMP; dying to go though. Have fun, just for hanging out and grabbing a beer, I've truly found a home at Buckley's (neighborhood bar) in Queen Anne .
Safe Travels!