The actual layout is generally done usually using VLSI (Very Large Scale Integration). This involves a lot of cell based design because it is impossible to layout by hand an entire chip. Most of the critical or basic circuit elements will be laid out by hand, that is, the physical layout of the silicon doping, metal layers, vias, pins, and etc are set out in a CAD software. From a large library of cells, the larger elements of a circuit are created. For example, if I needed a 32 bit adder for the ALU in my CPU, then I would first design a full 1-bit adder either by hand or by building up from logic gates from a library. Then I can cascade the 1-bit adders to make a 32 bit adder. This involves having some forsight in how I need to arrange the inputs and outputs of the full adder so that you can efficiently daisy chain them. And thus you have an efficient way of making a complex adder. They also need to route the innumerable number of interconnects between pins of different elements of the CPU. Again, the most critical ones are done by hand but most of them are done by computers using algorithms. These algorithms take into account such design aspects as time delays and area on silicon and they use various optimization techniques like simulated annealing to arrange the various circuit elements on silicon and route the various interconnects.
So a lot of the actual design of a CPU now is done by computers due to the immense complexity involved. But the most basic of the layout is generally done by hand and the design is hand tuned accordingly.