The fastest way is up through Seymour and across but I suggest you go through Healesville to the east (the sanctuary is unique in the whole country) and/or through Kinglake National Park (some beautiful hills covered in new growth forest - the area was hit pretty badly in the Black Saturday bushfires in 2009 and is still recovering - they could use your support). Some of Australia's most famous painters are from the stretch from Diamond Creek to Kinglake; and looking at the scenery you will realize why.
Hurstbridge, St Andrews and Kinglake are all cute old railway towns in the hills. Seymour is set by a lovely, deep, wandering river called the Goulburn (which waters most of Australia's pear farms) and there's a nice walk along the river's edge. Lake Eildon is pretty spectacular, too, on a clear day. almost 4 years ago