Note that I sign transaction offline. To put it simply your address is a private key, from which a public key (the public address) is derived. You can have one client, synced to the Blockchain, displaying your balanced, able to make transactions.
Then you take that transaction to an offline computer or source and sign it, take it back to the online computer and transmit it to the network. /roughly, see the other link for better information
Are you signing it manually? Or just doing some go-arounds with Bitcoin-qt? I'm really interested in this, but never found any python scripts or how-to's.
Look into the Armory client and some guides on how to do offline signing with it. It is also a deterministic wallet so your backups and offline computer will never run out of change addresses.
Then you take that transaction to an offline computer or source and sign it, take it back to the online computer and transmit it to the network. /roughly, see the other link for better information