The paging file is on the second drive. I didn't want it on the primary. If so many programs didn't look for it I wouldn't use it all. It's almost useless with 16GB RAM.
The problem with disabling the page file is that you don't actually have the ability to prevent Windows from paging. If you launch a program and it requests 768MB of RAM, Windows will give it priority for 768MB of RAM, even if it doesn't need to use it all right now. If the required commit charge of the active applications exceeds the available system memory, and there is no page file available, Windows will instead go about merrily evicting idle code that already lives on the hard drive somewhere -- program DLLs, for example. Depending on your system, these may be more fragmented across the drive than the page file would be, and thus slower to retrieve later. Contrawise, if a program requests a substantial memory allocation but doesn't seem to be using all of it at the moment, Windows may move some of that program's memory space to the page file in order to free up the system RAM for things that are active.
The likelihood of running into these situations depends on how you use your system, and what Superfetch is up to (assuming you're using Vista or 7). But in most cases, even if you have a large amount of RAM installed, disabling the page file isn't going to significantly change what Windows was going to do anyway. And even with 16GB of RAM, maxing things out isn't impossible. I've blown up 4GB without even trying (2GB RAM, 2GB page file) while manipulating high-resolution digital photos, for example.