According to the transaction fee rules, the size of the transaction is used to calculate fees (
https://en.bitcoin.it/wiki/Transaction_fees). From what I've read elsewhere, the size of the tx will be: 180 bytes per input + 34 bytes per output + 10 bytes.
However, while I've found that calculation to hold up most of the time, it doesn't seem to be accurate all of the time. Is there a more reliable way to know how large a transaction will be so that appropriate fees can be assigned when creating a raw transaction?
There is no way of knowing in advance how big the signatures are going to be. You can try making several transactions and based on the size of those figure out how large the fee must be.
You could also use a conservative estimate for the size and have users in some cases pay a little bit more.