Normaly the quickload program has given me good numbers and matches very close to the actual results I get in my rifles. I ran some numbers for my 375 H&H with a 270 TSX and it was kicking back some realy goofy numbers. Basicaly telling me that the max loads I was finding in the load manuals were anywhere from 10-25K PSI over pressure. I worked up to the max loads in the manuals with no pressure signs.

Anyone else experience this?

Not yet, Quickload has always been pretty much spot on for me. Did you contact the manufacturer of Quickload? They might either already have an updated file or the will want to fix it for their next updates. I would think they need to rely a lot on customer feedback to improve their product.

that was kind of in the list of plans for today.

The reasons of that inexactitude can be various; for instance, the case capacity and the bullet lenght, which affect the internal available volume of the case as well as lot-to-lot variance of powder canisters.

Many of todays guns have freebore whitch quickload cannot predict. I have played with weatherbies alot in the past and quickload has a hard time predicting them because of the freebore. When things like that come up I start putting my velocity into the program and "theorizing" how much more powder it will take to get to a certain speed. I just picked up a new rem 308 that has a ton of freebore. Quickloads guess with i4895 are on the spot with reloading manuals....yet my gun is producing speeds that are a full 2.5 grains weaker than it should. Probably a combo of a slow lot of powder and freebore. I'm thinking if you go to the range with the 375 and use the feature it has where it gives you plus and minus increments you can quickly see where you need to go with the next loads. It's all part of "working up" and quickload actually is a help and not a hindrance.
Oh yes...one feature that ql has the affects things alot also, is bullet seating depth. Anytime you seat a long bullet deep QL seems to really send pressure up faster than it is. In that 308 I talked about above I can seat a 180bt all the way to 2.800 or seat it so it is right at the rifling (which barely has the bullet in the case) and there was only 20fps difference at the range. Ql would have predicted a HUGE difference on that scenario.