The Murray in detail
Towns along the Hume Fwy are well serviced by V/Line trains (often in combination with bus travel). Having your own wheels allows you to explore country locations more easily, however.
V/Line also services the Murray Valley Hwy that runs alongside the Murray River.
Once you are in the Mallee region, you'll need your own car, especially if you plan to visit the national parks. Note: many national parks require 4WD.