In an interview with Kotaku, Bethesda's Todd Howard explained some of the reasons why The Elder Scrolls V: Skyrim worked without glitches for some people while others had huge problems.
"The way our dynamic stuff and our scripting works, it's obvious it gets in situations where it taxes the PS3. And we felt we had a lot of it under control. But for certain users it literally depends on how they play the game, varied over a hundred hours and literally what spells they use. Did they go in this building? [And so on.]", Howard explains.
The explanation that the issues may have to do with large save files is something Howard refutes:
"That's the common misconception. It's literally the things you've done in what order and what's running. Some of the things are literally what spells do you have hot-keyed? Because, as you switch to them, they handle memory differently...."
Hopefully, Bethesda can solve the issues for those who are experiencing problems.