Will having large numbers of Fields decrease site performance? I know that on page load Craft makes multiple queries to get Fields. I have about 300 separate fields on a pretty large site. I know it's probably better to reuse fields when I can, but in many cases I can't rename fields or field instructions so I wouldn't be able to name them semantically for the user. 

Is it OK to have this many fields on my site, or should I find another strategy to manage my large number of fields, many of which are very similar?
I can't answer your question directly as I never got even close to 300 fields yet. But even with 50 fields I had some serious slowdowns, especially when getting related entries in form of assets and such. 

I think you should definitely consider using the built in cache function to get good performance.

In regards to that field name / instructions problem you ran into, I can tell you that this is something I hope that gets changed in the future. I already made @Brandon Kelly aware of this problem and he probably has it on "the list".

.

Edit:

After thinking a bit more about this, I'd go with @Simon Kuran and believe that the number of fields have rather negligible moderate impact on your overall performance.

It's more about the numbers of DB queries and not that much about the amount of data they request.
Be careful with building and inquiring relationships in particular, as they can lead to many (unintentional) DB calls. But first and foremost: use caching. The {% cache %} tag is there for a reason! ;)