Rhythmic clicks from the wheel indicate faulty bearings at worst or just large pebbles stuck in the tread pattern at the best. A change in engine tone usually indicates engine overheating, especially if you have been driving at constant speeds for a long time. Stopping or varying the engine speed should be enough if there is no severe problem. Otherwise, let the car cool down and then check radiator and water levels. Backfiring while normal driving means serious problems and should be properly investigated.
Engine knocks means that it is time to get into a lower gear.
If it persists, however, it is time to get your engine and engine oil checked. At times, your car give personal signals which can be deciphered by only the user. Strange 'hiccups' while driving indicate faulty fuel which would in turn cause faulty carb or fuel injector. If there is unequal or wrong air pressure in tyres, it is evident on braking. Unexplained shudders in braking indicate problems in suspension or linkages.