Changing the format won't do anything. Like any program, Numbers only works in it's native format. It only imports and export the .xls files. Internally they are the same no matter what format it says when you save it.
The only thing I can suggest is to make sure you have as much free RAM as possible. Double tap on the Home button. When the multitask bar pops up dap an hold on an icon until it jiggles, then tap the minus sign to close it. This frees up any RAM that the app may have been using.
iOS keeps several recent apps in RAM, ready to start running again from where you left off. Some may even have a background task going, tho those should be limited to finishing a download, playing music, or updating locations (for map and tracking apps). Normally this is a convenience, allowing you to switch back and forth between apps quickly, however if you need maximum performance from the iPad closing them may help.
The list itself can be very long, since it will list pretty much every app you've used since the last time you cleared it. On an iPad 1, only the first 4 to 6 apps listed are normally still in RAM. I've seen as many as 18 still using RAM on the iPad 2.
There probably are ways to clean up a spreadsheet to make it run more efficiently, but I've little idea how to do this. Minimizing the number and complexity of formulas comes to mind, but I'm sure that would be a pain. If some of the worksheets are unrelated to the others (not needing to share data or be together for easy data entry) you could break the spreadsheet up into more than one document.
Try the clean up first, and if that does it, good. If not consider how you might be able to reorganize the spread sheet into separate documents that would still be easy to work with. Last resort would be recreating the spreadsheet with simpler and few formulas, if possible.
Also, one of the other Office style apps may handle the spreadsheet faster. Documents to go and QuickOffice are two of the most popular. Here is a
good summary by richsadams that might give you and idea of what you might want to try.