If you want significance overall... definately Mercury... just getting into space is the biggest achievement.
I voted for STS-107, for a different reason. Change comes about in great times of need and/or tragedy. September 11 is one example of this fact. World War 2 is another (UN was finally created).
The recent events will bring about a public/political need to
re-evaluate the effectiveness of the current space agency. In the last 4 years, 2 Mars orbiters/landers have crashed and the Challenger space shuttle destruction, costing taxpaying Americans billions upon billions of dollars. Every time the space shuttle is launched, it
costs $400 million dollars. It costs
$2 billion just to make the thing. They also wasted a
few million for a charter plane to Russia. Even though NASA launches often, they only command
20% of the commercial sector, a potential major source for profits.
The space shuttles are getting out of date. The concept is 20 years old. You can only slap new technology over the old designs for so long before the limitations shine through. Over the past 20 years, NASA has been trying to design new shuttles (8 to be exact),
but can't seem to get it right. They waste billions of dollars in the process.
I'm not saying the space program should be scrapped at all.
It should be re-evaluated. Management needs to be evaluated to figure out where the mistakes were made so they do not happen again.