Road Cycling - How much is too much "cross-gearing"?

I just replaced my 42T chainring with a 39 (I needed more granny gears for hills). Unfortunately, I've gotten used to the 42 as my main ring. Since the 39 is too "quick" for flats, I'll have to start using the 52 more, but I also want to keep a high cadence. What's the farthest I should go when I "cross gear"? I have a "14 speed" so only 7 cogs on the rear cassette. I know I shouldn't be "out/in" or "in/out" but that's only two combinations. Are those pretty much the only ones to avoid, or are there more?

As a rule of thumb I typically stay out of the two highest or lowest cogs when on the big/small ring respectively.

My favorite setup for flat to rolling and short 1 mile or less hills is a 53/39 with a 11-21 on the rear. The 39 actually gives me enough range from the 13 tooth cog up to climb alsmost any short steep grade with enough high gearing for maintaining 23-24 mph on flats at around 100-110 rpms cadence.

So when in the 53 I will stay off the 19 and 21 tooth cogs and on the 39 I stay off the 11 and 12. Occasionally I will use the 53/19 for short distances on low gradients but not very often.

it is easier to cross-gear the 9 and 10 speed cassettes than the 7's or 8's. i never did it before but when i graduated to the ultegra 9 speed the chain is a bit thinner and supported my cross-gearing needs.