Here is an example of how to make a poster when 2x2 is selected, and Overlapping Alignment Marks is selected in Print Cutting Guides.
Prepare Sheet 1 and Sheet 2. Cut off the margins of Sheet 1 along the vertical blue line through the center of the top and bottom cross marks.
Place the edge of Sheet 1 on top of Sheet 2 and align the cross marks, then temporarily tape the two sheets together from the back.
Cut the taped sheets in two along the vertical red line through the alignment markers (this time, the line to the left of the cross marks).
Tape the sheets together from the back.
Repeat steps 1 to 4 to tape Sheet 3 and Sheet 4 together.
Cut off the margins of Sheet 1 and Sheet 2 along the horizontal blue line through the center of the left and right side cross marks.
Place the edge of Sheet 1 and Sheet 2 on top of Sheet 3 and Sheet 4 and align the cross marks, and then temporarily tape them together from the back.
Cut the taped sheets in two along the horizontal red line through the alignment markers (this time, the line above the cross marks).
Tape the sheets together from the back.
Cut off the remaining margins along the outer guide.