Skip Gen 4 and/or Gen 5...

A LOT of stuff.
Two whole Galaxies

yes.

Gen 4 has a ton of potential all-stars with the abundance of cross-gen evos as well as some stupidly powerful legendaries.

Palkia and Dialga will be extremely strong. Same with Giratina and Arceus. Aside from legendaries, there are a ton of evolutions from previous Pokémon that will shake things up like Electrivire, Togekiss, Gallade, etc. You’ll be missing a bunch for sure.

You're going to miss the ebst pokemon in the series, gen VI (6)'s pokemon are completely trash (like the generation itself). Skipping gen IV and V would mean missing out on the 6 best dragon types in the game, 2 of the best pseudo legendaries, in gen IV theres a lot of pokemon that got mega evolutions that can be really strong, not to mention how a good number of pokemon got evolutions in gen IV, and those evolutions will likely outpace most lesser legendaries.

That and in gen V you'd miss out on machamp's replacement, and many many community days

You will miss Gen 4 and Gen 5

As an aside, I don't know if this is relevant still but an interesting read comparing Pokemon based solely off their base stats.
https://pokemongo.gamepress.gg/looking-ahead-ladder-best-pokemon-type

Gen 4 is the gen you DON'T want to skip.