The process which makes a major difference between $C_3$ and $C_4$ plants is:

Photorespiration is present in $C_3$ plants but absent in $C_4$ plants. $C_4$ plants minimize photorespiration by separating initial $C{O}_2$ fixation and the Calvin cycle by performing these steps in different cell types. This phenomenon occurs due to the RuBisCO enzyme's dual nature, which works on oxygenase activity if there is less carbon dioxide or more oxygen concentration.