From my previous post: "I suspect that the problem has more to do with ... coupled with some bug and/or poor choice of approach for making the calculation". This really only scratched the surface of possiblities and as much intended to point away from the qdf file size as it was to guess the exact cause of the problem. But ....
You admit you have a "boatload" of transactions; one way or the other, Quicken must find the "Sell" transactions (and possibly the capital gains distributions ... I don't know whether they are involved or not). One way to "find" the "Sell" transactions would be to read all the transactions ... which if you have a "boatload" of them, would take, perhaps, a "boatload" of time. While there are data base designs and programming approaches that could minimize that time, I point it out as being one of a number of possible "bugs and/or poor choices for making the calculation".