Depends on the total weight.
With tires mounted I usually do the following.
Cover face of wheel with thin flexible styro type sheet, then with 2 layers of cardboard. One layer of cardboard on the back side. Face centers towards each other and band 2 wheel/tire assembly's together. Learned this method from Tire Rack.
If just wheels I box them. Two wheels per box or band 2 boxes together.
Shipping 2 items is less expensive even if the 2 weight the same as the 4 as you pay a flat rate for each piece plus a modifier for weight and distance.
UPS or FedEx Ground have rates that are close. If possible, Greyhound has even better rates but require the receiver to pick up at their local station.