Two cards each 4.25" tall adds up to 8.5" the total width of your page. But few printers can actually print edge to edge. They often have a "printable area" less than 8.5 x 11 inches and thus your layout may not fully "fit" inside the printable area for your printer and thus you get one row of cards per page. If this is the issue, you'll need to reduce the height slightly in order to get two rows of cards to a page.
I guess what had thrown me off was the display in the 'Edit Layout' screen. I could only get one instance of my form letter to display no matter what I did with the margins / text box dimensions.
I resized the text box and now have all 4 cards displayed. Thanks for the help!