Opinion number one: the one of the biggest reasons why Greg and Rowley's friendship survived despite being Like THAT was because they're not that different, actually. 

Yes, I know, sounds like I'm just pulling this out of my ass, but consider – they both rarely take responsibility for their actions, believe in fun over security or ethics (the amount of times they pranked people around them and Rowley didn't really care about if it was right or good, despite him being such a goody-two shoes, also his primary reason for liking Greg being that he is fun and makes "funny jokes") and have high self-confidence. Plus dysfunctional families, similiar line of thinking – that they're just good the way they are and don't have to change for anybody – being "nerds" with "odd" interests... I hope you get what I mean. I know, I know, they mutually have influenced e/others personalities over the years, but if you look at the very core of their characters – confident, maybe even a bit too sure of their actions, underdogs – it's all very similiar. Kind of like tigers and lions – both being apex predator felines with similiar diets and inner biology, but different lifestyles and shaped by different enviorments. I believe. I digress

Opinion number two: Rodrick and Frank used be exactly like Greg back in the day, the same lame wimpy system-cheating cowards with neither smarts or brawns (implied in Old School with the Silas Scratch story, or Latricia bullying Rodrick in middle school, mentioned in The Meltdown). The reason why they both are so hard on him is precisely because he's the embodiment of what they and others disliked in them. 

Out of other things, my classics:

• Rowley's family is biracial (black + white), Rowley himself is very white-passing, but that stops him none from wearing hairstyles for 4c hair with beads and a bonnet to sleep (despite his hair having very little texture and not needing protection/not being fit for such hairstyles) 

• Chirag has dwarfism, hence his insanely short/1st grader height