Does knowledge of original file size provide a cryptographic weakness? I'm encrypting files using an AES-256 CBC cipher and an SHA-256 HMAC every 64KB in the file. Since AES CBC needs an amount of input bytes to be divisible by 16, I use PKCS#7 padding to bring the amount of bytes up to a count divisible by 16 at the end of the file. 

For this and for most cases of cryptography, does knowledge of the original file size expose a weakness enabling an attacker to gain an advantage in decrypting the data? If someone had knowledge of the way an encryption system works, it may be feasible for them to guess the original file size. Is this a problem?
Yes, feasibility to guess the plain text size might be a serious vulnerability in real life scenarios. For instance, in traffic analysis the approximate length of the messages in a communication, might reveal enough information about what is communicated, for it to be possible to deduce the gist of it. If such threats exist in your case, however, you will probably have to consider more radical counter measures than just apply a few byes of PKCS#7 padding at the end of your file fragments.