Subject to ratings of her own show the next companion I'd kill off would be Sarah Jane as it would have the biggest impact on both the Doctor and the audience.
If the Master was brought back and played by someone who actually looked like a convincing bad guy I think it'd be the perfect way to restore some of the characters original menace.
Failing that the new Daleks should do it.
She would have to come back over to Doctor Who for a few shows just to ween her in then BAM! dead!
I thought John Simm was a great enemy but it got so silly when he turned into the Who equivilent of Darth sideous with his force lightening. Plus i always thought the Docotrs rise from being years old in the last of the time lords and floating around before using his big weapon of 'i forgive you' was the cheesiest thing i had seen.