Are these thread colours that you would use again? If so, I would definitely bite the bullet and get the large cones of at least three colours, making sure that they are the ones with the largest area in the quilt, and assuming I can use them in other areas if I run short. If no substituting can be done, or they really are all equal, I would get the large cones of all.
I try to do risk/benefit analysis in these cases: I would be mildly disgruntled about paying twice as much for the thread. On the other hand, if I ran out, had to reorder, then wait for it to come in, and waste money on a second shipping charge, I would be really, really unhappy. So, I would pay up front to avoid the possible annoyance later.
At your Isacord prices, you're spending an extra $24.50 to get the 5000m spools. To me, the hours you're going to put into quilting this thing are worth way more than that. And you're getting an extra 28000m of thread... the more I think about it, the more the sure I am that the big spools are the way I would go!
This sounds like it's going to be an amazing quilt. Be sure to post pictures when you get it done!