English is very lopsided about which pairs occur. TH, HE, IN, ER and AN cover a large share of everything you type, so a layout that places those pairs badly costs you on almost every sentence, while one that places rare pairs badly costs almost nothing.
The comfortable case is a roll: two letters on adjacent fingers of the same hand, typed in one inward motion. The uncomfortable case is a same-finger bigram, where one finger has to leave a key and hit another before the next letter can go in. Alternative layouts such as Colemak-DH are built largely around reducing that second case.
Bigrams are also why speed comes back unevenly after a keyboard change. Frequent pairs get retrained by sheer repetition within days; rare ones can still trip you up weeks later.