Before embarking on a large BLAST experiment, first try some pilot experiments. For example, if you want to compare all human proteins to all nonhuman proteins, try 100 proteins first. Or, if you want to annotate a 5 mb chromosomal region with BLASTX similarities, search 100 Kb first. If you're unsure of which parameters to use, try several and see which ones give you the kinds of results you're looking for. It may seem like a waste of time, but performing pilot experiments will actually save you time in the end.