Everyone has a different opinion on if you should keep writing those big popular grants that you haven't been successful in receiving year after year. As someone who has been in roles dedicated to writing, researching and following up on grants, I always thought to write any and all grants that fit the cause. I am of the mind set that you should always apply if you have the ability too, unless you are told by the funder not too.
You never know what a funder or a panel is going to find interesting or what they might think is worth funding this time around. There really is no harm in trying, because nothing bad comes from just applying for a grant. Now this doesn't mean I think you should always send through the same application or apply for the same program. If you are going to reapply, you need to change it each time. Aim to make the application a little bit better by using a new program that might be a better fit, rewording the content so it reads smoother and conducting more research. To be successful you need to improve your application otherwise you will continue to be unsuccessful for the same reason. If you can get verbal or written feedback, always accept it because that is the best way to improve. The larger grants commonly don't provide any feedback, in this case, you need to be critical yourself. Reread the guidelines, see what other programs were successful, figure out what didn't work and then try again in a new way.
Give anything a shot because you never know what will be successful and a written application never goes to waste. It is still written content that could help you reapply for another grant. Also, writing more applications helps you get better at writing, understanding the program and building an inventory of content for other uses. By writing one application you can save yourself time on future applications for the same program. I regularly reuse grant content because I know it was written well or the application is asking the same questions. So having an inventory of content will save you time and effort in the future.
If you have a different role and grant writing is only a part of it, I have a different opinion. Sometimes you have limited time, there might be multiple grants open and your time might be better spent somewhere else. In that case, don't waste your time on an unlikely grant. Prioritizing grants is a better way to dedicate limited time. Using a matrix and classifying which grants are low and which ones are high priority, is a good way to decide what to apply for. Plus this provides you with a justification of why you passed up a larger grant.
I have always thought when you have the time, applying for more grants is better. On average, people are successful with about 20% of submitted applications, so the more you apply for the more success you have. As well as, the more written content you have in your inventory, the more content you can reuse. So for those of you who are tossing up whether or not you should apply for that IMPACT Perpetual grant or that Ian Potter grant, give it a shot! You have nothing to lose and you never know what the outcome could be.
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