I routinely use 30gb truecrypt folders, and I have a 300gb USB disk that I encrypted completely. I don't see any performance issues. It does take some time to do the initial encryption, and that time seems to be linearly dependent upon the size of the encrypted object.
I believe that either truecrypt approach (files / disk) will make it impossible for anyone to read the disks. My concern would be backup of the data and whether when backing up the information was unencrypted.
Having the disk entirely encrypted, provides some added security in that nobody can easily copy the encrypted information and then set machines to break the encryption on the copy. However, having the disk encrypted means that copying the data even to another encrypted disk means it is being transmitted as clear text. It also means that you can't backup the information very easily to some other disk.
I think if you pick a reasonably good AES key, then the probability that a copy of the encrypted information will be broken is really really small. The backup capability is really worthwhile, because the probability of a disk failure is higher than the probability of breaking the encryption. This means I would go with an encrypted folder and come up with some backup solution.
The amount of work to access the encrypted information is about the same in both cases. I thought that truecrypt would ask me for the password when I plugged in my encrypted disk. However, I have to access the encrypted information in the same manner whether the disk is encrypted or the encrypted information is in a folder.