Is anyone else a bit... struggling with the new controls?

This changes everything. Haven't used mantle much because CTRL is so awkward to use and I didn't want to waste another "good" key for that. Thanks for the tip.

That's why I ultimately switched handedness (I'm generally right-handed but was using the mouse with the left). Was a bit weird at the start but I felt comfortable really quickly. 

Best advice I've seen so far, I'm going to do this.

I have a gaming mouse with 3 side buttons.  I've mapped those to 1, 2, and 3 for easy power use.  I mapped reload to mouse wheel down, which is what I used in ME3.  Since we no longer have reload cancel, I have mouse wheel up to "F" for melee attacks.  Sprint, mantle and jump have been my big problems, I can never seem to hit the mantle button.  So I'll put them both on the space bar.  Now I just need an easy key for jump, since it gets used a lot.

Tempting to remap the missiles, etc to the old keys from ME3, if it lets you.

I'm really thinking about binding mantle+sprint on space now, but where do you put jump then, shift? Probably worth a try.

For those that played MP, how often do you have a use for jump there? (there's a lot of jumping in SP and I like using space + mouse wheel for jump dash combo) atm).

I really hate pressing LB+RB (or L1+R1) for the 2nd power. Melee on Y is also stupid.

I only bind evade to my mouse upper thumb button and medgel to lower thumb button and playing as a Human Vanguard, the controls and feelings just grow on me.

Isn't middle mouse button too cumbersome and slow to press for something as important as dodge? At least on my mouse it is. I would actually consider switching this with the jump, or just not use it at all in my case.

Oh god, it's going to take me another 3 years to get these old fingers to learn new habits

I am still not happy with Sprint on Toggle. Either I am tapping it too light or it ignores me, because it just knows. The only thing that seem to reliably stop my sprinting is running into a wall. I guess, i am gonna try going back to holding it down to Sprint.

So, is Mantle basically for vaulting over the obstacles? If so, i am so rebinding it to the Evade...

I use Shift for Sprint and Mantle, V for camera swap/look, Ctrl for Dash, B for holster, Q for ability 1, Alt for ability 2, Mouse 4 for Ability 3. The reason for changing the ability keys is some abilities require/allow holding the button, which is awkward to do with 1/2/3 keys while also moving with WASD. Took a bit of getting used to but now I feel as much in control as I did in ME3 (except with better mobility and verticality).

UPDATE:

After reading some suggestions and reading in the thread (thanks guys), and some experimenting I have to down to what I think is the optimal scheme for me, and might be useful for someone else as well.

Do note, I'm using a Roccat Tyon but most of the extra buttons are used for utility in SP like scanning, squad orders and menu shortcuts. What matters is the general control scheme that works both for MP and also without changing anything remaining fully functional for SP so the transition is seamless. Also to note, one of the very important controls I learned is Camera swap which main purpose I suppose is to switch leaning focus in cover between left/right, it's something I saw some other people asking here on how to do, so I'm throwing that out there.

The point of this keybinding is to stay as close as possible to original ME3 while putting important controls that you have to use mid-combat in such places, that it does not block your from movement (WASD) or aiming (pressing inconvenient mouse buttons during shooting is not great for your aim).

Sprint and Aim are on HOLD, Powers on TOGGLE (like ME3 flamer style, can move while flaming)

Camera swap - CTRL or ALT (you have one of those free in my setup, I used ALT for walking in SP)
Sprint and Mantle - SPACE
Jump - SHIFT
Dodge - MOUSE WHEEL DOWN
Melee - MOUSE WHEEL UP
Reload - MOUSE THUMB
Switch weapon and holster - MOUSE SIDE BUTTONS (to your preference), alternative we could use up ALT or CTRL here, but do people still run two weapons?
Abilities - Q, E, R (I'm used to this from all games)
MP items - 1,2,3,4 (I'm used to this from ME3)
Interact - F or C (works better for me than CTRL/ALT)
(SP) Weapon wheel - MIDDLE MOUSE (I don't know how this works in MP yet, but I use it to activate ammo powers and cons)

This covers the main controls, the others are for SP and are not as important, what is important is that between the two the main remain the same.

For the SP I help myself with putting a lot of utility controls on the mouse, or just use keyboard shortcuts.

A simple control list may doesn't look like much, but I tried many different combinations with switching all these everywhere around, and came to conclusion that no combat ability like dodge or melee should be put on a position where you would have to move one of the fingers that are on WASD. Once I actually played with this scheme for a bit, everything came together really well this time.

For example, having both dodge and melee on a mouse wheel enables you to quickly and easily execute dodge + DFA air combo without having to press anything else on the keyboard besides shift for jumping, and holding space for sprinting while still having 100% uptime on your WASD movement, those fingers never move except for power uses, so you can be fully mobile at all times, dodging and shooting with just the main mouse buttons, mouse wheel on right hand, and left hand sticked to WASD with pinkie glued to SHIFT - jumping and thumb to SPACE - running and climbing.

If you're still trying to find a good scheme for yourself I suggest you try this one, I really like it the most and probably won't be changing it anymore.