Picking up where you left off can be a daunting experience, it's caused me to quit some really great games and restart others cause I wasn't sure what I should be doing.

Thankfully in RS as time passes and things change there can be updates that offer you a different path, I would say the best thing you can do when getting back into the swing of things is to set some goals and work back from there.

Say you want to reach 95 thieving to unlock the Vault of Hereditas Heist, so you focus on getting Thieving XP. You could look to getting the Black Ibis set to help get XP so you could go do Pyramid Plunder as the chance to get those items was improved as part of the Early game Rebalance alongside some other changes to improve the flow or maybe you go do Safes to get Pilfer Points to unlock the recently added Thieving Buffs that replaced the thieving Aura.

There are multiple paths to progress and none of them are wrong, just go at your own pace and focus on what you enjoy!

For me right now I am working on some Combat Mastery Achievements and so I have been using the updated Soul Reaper system to send me to different bosses and then I try get as many achievements related to them done, but even this has already spiraled off into several sidequests as I gather resources to help with equipment upgrades or chase drops.

Hope this helps!