If you're buying as a collector, you should buy the book at a grade and price you're comfortable with, knowing that you'll still enjoy owning it even if it becomes worthless in the future.
If you're buying as an investor you need to think about what you want to get out of owning the book, and decide which grade and price best fits your strategy.
Even though the market for many books is on an incredible tear right now we can't say with absolute certainty how things will be in the future...
If you're bearish on Spidey #300 it may make more sense to pick up a nice-presenting lower grade copy as several boardies have already suggested. This way, if prices fall you'll have less invested into the book, and if prices rise you should be able to trade up to a nicer copy because your copy will be worth more.
Regardless of what you decide, good luck with the hunt!