The M60F will be brighter. I don't know how relative a "substantial" difference is to someone else, but yes, it will be noticeably brighter when compared side by side. The beam will be a bit smaller, and more concentrated(though still a great flood), and I think the integrated diffuser lens is more efficient than the F04, allowing more output.
The E2DL with F04 will have a wider beam, just not as bright. I like the versatility, and that it's a compact package with a clip. It draws about 510mA from 2xR123 vs. 550mA for the M60(don't remember what they draw from primaries), so the difference in runtime will be negligible. The E2DL on low will draw ~20mA on 2xR123, but I don't know about the low on the Malkoff MD2 with resistor ring, since I don't have one, and haven't done the math.
Another option if you don't care about having two levels is to buy a E2e-BK/E2D/E2DL body on the Marketplace and your choice of tailcap, then add a Malkoff VME bezel with your chosen Malkoff drop-in. I have a M60WLF set up like that, and really like it. It will be basically the same size as your E2DL, but shorter and a little heavier.
Think I have some beamshots posted somewhere around here showing the M60W with diffuser, M60WLF, and M60WF, and will try to find the thread. My favorite is the M60W with FM34 diffuser, and that is what I use at work.
edit:
http://www.candlepowerforums.com/vb/showthread.php?t=202448
In response #11, the shots in the middle and on the right should be fairly representative of the difference you will see between the E2DL/F04 and M60F. Unfortunately they're just wall shots. The M60WF was actually brighter than I needed, and I put it in a 6PD for my friend who posts here as "Robocop" to use indoors, for vehicle searches, and stuff like that on duty.
I would never dissuade anyone from buying a Malkoff, as Gene and Cathy seem like great people, and they put out great products, and offer great customer service(so buying from them is a win, win, win), but the F04 is worth getting, even if you do buy a M60F and host as a dedicated flood light.