I'm pondering this with my big doors on my barn. One thing I did already was put a toggle clamp on the jamb on each side. It engages a U-bolt on the door, allowing me to pull the door fairly tight against the opening once the door is closed. I've thought about buying strip brushes and attaching them around the edges. I'll never get my 12' tall doors really tight, but I'd like to at least be able to keep mice out.
If you don't open them a lot, you could buy/make a soft door seal to lay on the floor inside. Basically, it's a long cloth tube filled with something heavy enough to hold it in place. Simply move it out of the way when you need to open the doors.
One thing I've considered is a big vinyl sheet, installed semi-permanently over the opening. I'd put it in place when it started getting chilly, and remove it in the spring. They make big roll-up insect screens for big doors that run in a track on each side. I would think the same thing could be done with heavy vinyl.
The other issue I have is rain. When it hits the wall the door is on, it pours down the inside of the door like a waterfall. I made a wide flashing and put it over the track which helps, but if it's really windy, I still get water inside. I'm going to build a 4' deep shed roof over the entire door track, which will solve that problem.