This is easy to do in PIL too. Create an empty image and just paste in the images you want at whatever positions you need using paste. Here's a quick example:
import Image
#opens an image:
im = Image.open("1_tree.jpg")
#creates a new empty image, RGB mode, and size 400 by 400.
new_im = Image.new('RGB', (400,400))
#Here I resize my opened image, so it is no bigger than 100,100
im.thumbnail((100,100))
#Iterate through a 4 by 4 grid with 100 spacing, to place my image
for i in xrange(0,500,100):
for j in xrange(0,500,100):
#I change brightness of the images, just to emphasise they are unique copies.
im=Image.eval(im,lambda x: x+(i+j)/30)
#paste the image at location i,j:
new_im.paste(im, (i,j))
new_im.show()
