The size of the file is not the problem, it's the speed of the user's connection. I can upload a 100MB file from my fast connection at work because it will take less than 135 seconds. I can't do it from home on my slower connection because the page will time out.
We have fixed this for now by increasing the timeout setting in IIS 7 for the site. You don't have to do this normally? How else would you avoid the timeout issue for very large files? Is the control itself supposed to be able to set timeout values somehow? We have the trust level set at full already. Does the control need to be able to modify a setting that may be locked at the machine.config level or something like that?