Not only does Doom's origin have to be made part of the story somehow, it also seems that the FF's origin needs to have a strong connection to it as well. I hate it when origin scenes comes off as "bonus scenes that don't really have anything to do with the main story."
This is a bit specific, but simply meant as an example:
Start out with a mother or older sibling of a poor family telling some youngsters the tale of the ruler of their country... a ruler known as Victor Von Doom. Going into how his mother was apparently abducted to another dimension by some kind of extra-dimensional being which may or may not be a "demon". How Victor left his country to find a way to get her back. "Some say he sought answers in mysticism, the dark arts, some say he sought it in science. Maybe it was both."
This would then transition into a time period set in the past, when Victor goes to the same University as Reed. We'd get a introduction the Sue, Ben and Johnny as well, and the idea that Victor is trying to find a way to punch through to other dimensions (to find and save his mother). His experiment goes wrong however, and leaves him terribly scarred. He blames Reed, who had warned Victor about perceived errors in his calculations.
Flash forward to the present. A bunch of powerful creatures/monsters have been showing up all over the world, and a joint effort, under the supervision of Reed Richards to find the cause has led to Reed and his friends working at a space station in orbit around the Earth, trying to intercept "energies" that Reed suspects are what forms/causes the monsters. Something goes wrong (due to sabotage we'll later find out) and the Fantastic Four are formed.
For a while they are heroes. They travel the world doing battle with these creatures, while Reed is to find out where they're coming from.
It is then revealed that these monsters are being pulled from other dimensions as a side-effect of new experiments performed by Doom. The accident that formed the FF was sabotage in order to stop their research, again Doom's work.
The conclusion would have Doom lure the FF into the parallel dimension with the demon in it, and force the FF to help Doom fight this demon. In the end the FF manage to escape before the portal to this dimension closes, with the last we see of Doom being him stubbornly struggling alone against the demon. Very likely captured there, locked in battle "forever".
Something like that (in spirit, and in how it connects the different story lines). I'd have the film imply Doom's connection to mysticism and dark arts, and have him perform some amazing things... but have it so that you could assume he's using advanced technology.
The story would have to both feel "epic" and still have a sense of fun and humor.
Clearly you have to sacrifice some of the faithfulness when it comes to story in order to make it work, but personally I wouldn't mind it as long as the spirit of it is intact.
