Just thinking about this now.. as I just cured the genophage.
This is second time through and both times I cured it.. just about didn't this time but did at last minute inside the Shroud I thought it was too late because I didn't interrupt wrex when he did his whole Hero speech... but the final talk with Mordin did feel hollow.. he's just like.. "ok whateves"
But for ME2 I always saved the Collector base.. and in ME I always saved Wrex.
Most of my major decisions are Paragon. My pure Renegade playthrough is the first and only time I've made certain Renegade decisions such as sell Legion, keep the Collector Base and sabotage the Genophage cure. I've been very much tempted to let the Council die in ME1 on many of my Paragon playthroughs but I usually end up saving them anyway.
For non-critical dialogues and decisions I often pick Renegade options if I think it fits the situation or has the best result. I always punch the quarian Admiral in the stomach after he tries to blow me up. During Samara's recruitment mission in ME2 you meet this one Eclipse merc who tries to play herself off as an innocent bystander in over her head. You can kill her or let her go. Since you later find out she is a murderer I always just kill her and be done with it.