When using your effects loop, how you drape your cables can make a huge difference in your tone.
Amplifier transformers can induce hum into guitar cables that are too close to them. Avoid running cables over the top of the amplifier or close to the side of the amp by the output power transformer. Run cables straight down from the effects loop and along the bottom of the amplifier to avoid ground hum in your guitar signal. Always use high quality, shielded guitar cables.